Tandem Pd/C-catalyzed reductive coupling and dehalogenation of benzylic halides

Article abstract of DOI:10.1080/00397910500214458

High-yield reductive homocoupling of benzotrichloride and benzal chloride followed by consecutive reductive dechlorination to 1,2-dichlorostilbene and stilbene is effected in the presence of sodium formate as the reducing agent and Pd/C catalysts. Copyright Taylor & Francis, Inc.

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Tandem Pd/C‐Catalyzed
Reductive Coupling and
Dehalogenation of Benzylic
Halides
Ashutosh V. Joshi a , Mubeen Baidossi a , Nimer Taha
a , Sudip Mukhopadhyay b & Yoel Sasson a
a Casali Institute of Applied Chemistry , Hebrew
University of Jerusalem , Israel
b Department of Chemical Engineering , University
of California , Berkeley, California, USA
Published online: 22 Aug 2006.
To cite this article: Ashutosh V. Joshi , Mubeen Baidossi , Nimer Taha , Sudip
Mukhopadhyay & Yoel Sasson (2005) Tandem Pd/C‐Catalyzed Reductive Coupling and
Dehalogenation of Benzylic Halides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 35:20, 2715-2722
To link to this article: http://dx.doi.org/10.1080/00397910500214458
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Synthetic Communicationsw, 35: 2715–2722, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500214458
Tandem Pd/C-Catalyzed Reductive
Coupling and Dehalogenation of
Benzylic Halides
Ashutosh V. Joshi, Mubeen Baidossi, and Nimer Taha
Casali Institute of Applied Chemistry, Hebrew University of Jerusalem,
Israel
Sudip Mukhopadhyay
Department of Chemical Engineering, University of California, Berkeley,
California, USA
Yoel Sasson
Casali Institute of Applied Chemistry, Hebrew University of Jerusalem,
Israel
Abstract: High-yield reductive homocoupling of benzotrichloride and benzal chloride
followed by consecutive reductive dechlorination to 1,2-dichlorostilbene and stilbene
is effected in the presence of sodium formate as the reducing agent and Pd/C catalysts.
Keywords: Base, benzylic halides, homocoupling, Pd/C, reducing salts
INTRODUCTION
C-C bond formation via homo- or heterocoupling of alkyl and aryl halides is of
considerable interest in modern organic synthesis.[1] Stilbene and bibenzyl,
which are used as intermediate compounds in the production of dyes,
paints, and resins, are generally synthesized by homocoupling of benzyl
halides in the presence of a stoichiometric excess of a metallic reducing
Received in the USA April 28, 2005
Address correspondence to Yoel Sasson, Casali Institute of Applied Chemistry,
Hebrew University of Jerusalem, 91904, Israel. E-mail: ysasson@huji.ac.il
2715

2716
A. V. Joshi et al.
agents. Commonly used agents include Ni,[2] Mg,[3] In,[4] Fe,[5] Mn coupled
with CuCl2,[6] and Zn coupled with Cu[7]; salts and carbonyl complexes[8]
of Ni, Co, V, Mo, and Fe have also been used. In a different approach,
benzal chloride and benzotrichloride have been coupled and reduced to benzo-
thiophenes when heated with sulfur[9] at high temperature. With the exception
of a recent report, which describes a catalytic electrochemical process,[10] the
various techniques disclosed hitherto for the coupling of benzylic halides all
require the utilization of a stoichiometric amount of a reducing metal.
However, having considered the environmental impact of the use and
disposal of these toxic reducing reagents, there is incentive to find a cleaner
catalytic alternative for these reactions.
We have previously demonstrated the unique activity of the Pd/C catalyst
in the reductive homocoupling of aryl halides to biaryls in the presence of
formate salts using water as the solvent.[11] In this article, we describe the
application of this scheme to the reductive coupling of benzyl chlorides to
bibenzyl derivatives. The reaction is particularly effective for the coupling
of benzal chloride and benzotrichloride to yield stilbenes.
RESULTS AND DISCUSSION
In a typical reaction, a mixture of 1.6 mmol of benzotrichloride (313 mg), 4 ml
of dimethoxyethane (DME, solvent), 1.9 mmol of sodium formate (129 mg),
2.5 mmol of sodium carbonate (265 mg), 23.5 mmol of 5% Pd/C catalyst
(50 mg), and biphenyl (50 mg as an
internal standard) was stirred at 1208C in a sealed pressure glass tube for 3 h.
GC analysis of the reaction showed 100% conversion. 1,2-Dichloro-1,2-
diphenylethylene (1, 87% GC yield, 7 : 3 E : Z ratio) with inorganic
products, namely, sodium chloride, carbon dioxide, and water, were
obtained (Eq. 1). Some toluene is formed as a result of competitive hydro-
dehalogenation of the substrate.[12]
The results are reproducible (Eq. 1) within 1.5% error margin and repli-
cated exactly with almost the same results when scaled up to 10 times the
original batch. The GC yield of 1 was around 85–86% at 100% conversion
level. Similar results were obtained when 4-chlorobenzotrichloride was used
as the substrate. Neither aryl-aryl bond formation nor aryl-alkyl bond
formation were observed, suggesting that the benzyl C-Cl bonds are far
more labile to the coupling process than the aromatic chlorides under these
reaction conditions.

Benzylic Halides
2717
The progress of reaction in Eq. (1), as monitored by GCMS, indicates that
the formation of 1 is taking place in two consecutive steps: direct reductive
coupling via activation of the benzylic C-Cl bond followed by reductive deha-
logenation of the intermediate to yield 1. The first step of the sequence was
isolated from the rest by eliminating carbonate base from the reaction
blend; the observed conversion rate was significantly slower and after 8 h of
reaction time, an 85% yield of 1,1,2,2-tetrachloro-1,2-diphenylethane (2)
along with 8% of 1 and 6% toluene were obtained. The process can be
written as follows (Eq. 2):
The slow reaction rate in reaction 2 was attributed to the formation of
hydrogen chloride, which affected the performance of the catalyst by
reacting selectively with the active Pd(0) clusters.
The coupling product 2 was readily converted to 1 via reductive dehalo-
genation. Thus, heating 2 at 1208C for 3 h in the presence of formate and
carbonate salts, DME, and Pd/C resulted quantitative yield of 1 (Eq. 3).
Comparable results were obtained when benzal chloride was treated
under these conditions. Thus, when benzal chloride was exposed to the con-
ditions of reaction 1 for 7.5 h, 61% stilbene (3) was obtained along with
hydrolysis (benzaldehyde) and hydrogenolysis (toluene) products (Eq. 4) at
100% conversion level.
Analysis of the reaction mixture in the early stages of the reaction
revealed that the expected intermediate, 1,2-dichloro-1,2-diphenylethane (4,
Eq. 5) (1 : 1 dl/meso ratio), appeared momentarily (reaching a maximum of
42% after 3 h) and eventually converted to 3.
Benzyl chloride reacted in a similar way; however, it was found to be far
more susceptible to the competing hydrogenolysis reaction, yielding toluene

2718
A. V. Joshi et al.
as the major product. As a result only 18% yield of bibenzyl (5) was obtained
at complete benzyl chloride consumption level (Eq. 6).
Even though a carbene mechanism was proposed previously for the
metal-promoted coupling of benzotrichloride,[3] we were unable to trap any
of these intermediates using a cyclohexene scavenger. Evidently, addition
of a radical scavenger such as hydroquinone significantly inhibited the
progress of reactions 1, 2, 4, and 5; therefore, we propose that these
reactions proceed via a single-electron transfer process resembling the
mechanism we have put forward for the Pd/C-catalyzed reductive coupling
of aryl halides in presence of formate salts.[13] According to the latter, two
neighboring palladium sites are oxidized through a one-electron transfer to
the substrate, resulting in a chloride anion and an adsorbed a,a-dichlorobenzyl
radical (Eq. 7):
II
_
2PhCCl3 þ Pdð0Þ ꢀ! 2PhCCl2 þ Pd Cl2
ð7Þ
The radical species then dimerize to yield dibenzyl derivatives (Eq. 8):
_
2PhCCl2 ꢀ! PhðCl2ÞC-CðCl2Þ-Ph
ð8Þ
2
Finally, the PdII species is reduced by the formate salt to Pd0, which
initiates a new catalytic cycle: (Eq. 9):
PdIICl2 þ HCO2Na þ H2O ꢀ! Pd0 þ 2HCl þ NaHCO3
ð9Þ
The reduction with formate salts requires stoichiometric amount of
water[14] and no reaction (1–6) progress was asserted by GC unless a small
amount of water was present in the system. However, once the reaction
starts, water is generated in situ via neutralization of HCl with added
carbonate base.
Interestingly, the reducing power of formate salt was further utilized in
reaction 1 (Eq. 1) when four equivalents of it was added to the system and
the mixture was maintained at 1208C for 20 h. The major product was iden-
tified as bibenzyl. We propose that a four-stage catalytic reductive cascade
reaction is taking place in the following sequence (Eq. 10):

Benzylic Halides
2719
Reductive coupling in the first step is followed by reductive dehalogena-
tion, which involves electron transfer from the metal to the substrates.
Subsequently, the resulted dichlorostilbene undergoes hydrogenolysis in
the third step followed by its hydrogenation to bibenzyl in the final step.
The last two steps require hydrogen atoms; formate salt acts as the
hydrogen donor.
EXPERIMENTAL
Melting points were measured in glass capillaries using an Electro thermal
1
9100 instrument. H NMR spectra were measured on a Bruker AMX 300
instrument at 300.13 MHz. GC and GCMS analyses were performed using a
HP-5890 gas chromatograph with a 50% diphenyl–50% dimethylpolysilox-
ane packed column (25 m ꢁ 0.53 mm). Unless stated otherwise, chemicals
were purchased from commercial vendors (.98% pure) and used as such
without further purification. Products were either isolated and identified by
1
comparison of their H NMR spectra with standard samples, or identified by
MS data and comparison of their GC retention times with standard samples.
1,2-Dichloro-1,2-diphenylethylene (1) was prepared by reducing
1,1,2,2-tetrachloro-1,2-diphenylethane (2). One mmol of 1,1,2,2-tetrachloro-
1,2-diphenylethane (320 mg), 10 ml of THF, 2 mmol of sodium formate
(136 mg), 2.5 mmol of sodium carbonate (265 mg), 3 mmol of water
(54 mg), and 23.5 mmol of 5% Pd/C catalyst (50 mg) were mixed in a glass
reactor and stirred under vigorous agitation at 1208C for several hours.
After a stipulated period of time, the mixture was cooled and the solids
were separated by filtration (the catalyst was washed several times with hot
methanol and reused). The filtrate was distilled under reduced pressure to
isolate the solvent from products. Crude 1,2-dichloro-1,2-diphenylethylene
(1) (230 mg, 90% GC yields) was obtained, which, on recrystallization from
methanol, gave 212 mg (85% isolated yield) of pure material. The isomers
were separated by preparative chromatography. cis-Isomer Mp ¼ 64–668C
(pentane); NMR (CDCl3) g 7.18 (s, Ar, 10 H). Anal. calcd. for C14H10Cl2
(248.02): C, 67.49; H, 4.05; Cl, 28.46. Found: C, 67.45; H, 4.05; Cl, 28.50.
trans-Isomer: Mp ¼ 141–1428C (ethanol); NMR (CDCl3) g 7.30–7.75
(s, Ar, 10 H). Mass (m/z) 248, 233, 213, 195, 178, 152, 89. Anal. calcd. for
C14H10Cl2 (248.02): C, 67.49; H, 4.05; Cl, 28.46. Found: C, 67.45; H, 4.05;
Cl, 28.50.
1,1,2,2-Tetrachloro-1,2-diphenylethane (2) was prepared by reacting
1.6 mmol of benzotrichloride (313 mg) in 4 ml of dimethoxyethane (DME,
solvent) with 1.9 mmol of sodium formate (129 mg) in the presence of
23.5 mmol of 5% Pd/C catalyst. The reaction mixture was stirred at 808C
for 8 h. An 85% yield of 1,1,2,2-tetrachloro-1,2-diphenylethane (2) along
with 8% of 1 and 6% toluene was obtained by GC analysis. The reaction
mixture was then cooled and filtered, and solvent evaporated under reduced

2720
A. V. Joshi et al.
pressure to obtain 0.203 g (80% isolated yield) of crude 1,1,2,2-tetrachloro-
1,2-diphenylethane, which upon recrystallization from acetic acid gave
almost 180 mg of pure, white, crystal material, Mp 160–1628C; mass
(m/z): 283, 247, 212, 195, 178, 159, 89. Anal. calcd. for C14H10Cl4
(317.95): C, 52.49; H, 3.12; Cl, 44.32. Found: C, 52.48; H, 3.25; Cl, 44.00.
NMR (CDCl3) g 6.90–7.67 (m, Ar, 10 H).
trans-Stilbene (3) was synthesized from benzal chloride by refluxing a
mixture of 1.9 mmol of benzal chloride (305 mg) in dimethylacetamide
(DMA) solvent at 1208C oil-bath temperature in the presence of 1.9 mmol
of sodium formate (129 mg), 2.5 mmol of sodium carbonate (265 mg), and
23.5 mmol of 5% Pd/C catalyst. After 7.5 h, a 61% yield to trans-stilbene
was obtained after workup and crystallization as stated previously. Mp
122–1238C; mass (m/z) 180, 165, 152, 115, 102, 89, 76, 63, 51. Anal.
calcd. for C14H12 (180.09): C, 93.29; H, 6.71. Found: C, 93.25; H, 6.75.
1,2-Dichloro-1,2-diphenylethane (4) was prepared from benzal chloride
by heating a mixture of 1.9 mmol of benzal chloride (305 mg), 1.9 mmol of
sodium formate (129 mg), 2.5 mmol of sodium carbonate (265 mg),
23.5 mmol of 5% Pd/C, and dimethylacetamide (DMA) for 3 h at 808C.
After workup, a 42% yield to product was realized. Mp 191–1938C; mass
(m/z) 250, 215, 195, 178, 165, 152, 125, 115, 99, 89, 76, 63, 51. Anal.
calcd. for C14H10Cl2 (250.03): C, 66.95; H, 4.82; Cl, 28.23. Found: C,
67.45; H, 4.05; Cl, 28.50.
1,2-Diphenylethane (5) was synthesized from benzyl chloride by
refluxing a mixture of dimethylacetamide (DMA), 1.9 mmol of benzyl
chlorides (240 mg), 1.9 mmol of sodium formate (129 mg), 2.5 mmol of
sodium carbonate (265 mg), and 23.5 mmol of 5% Pd/C catalyst in a hot oil
bath at 1208C. After 7.5 h, a 18% yield to product was obtained. Mp 51–
528C; mass (m/z) 182, 165, 152, 115, 104, 91, 77, 65, 51. Anal. calcd. for
C14H14 (182.11): C, 92.26; H, 7.74. Found: C, 92.20; H, 7.77.
CONCLUSION
We have successfully demonstrated a simple, high-yield catalytic process for
the coupling of a-halogenated toluenes to bibenzyls and stilbenes. The trans-
formation of benzotrichloride to 1,2-diphenylethane is studied in detail and it
is realized that the reaction proceeds in four distinct steps, starting with
reductive coupling at the first step followed by reductive dehalogenation at
the second, which involves electron transfer from the metals to the substrates.
Subsequently, in the third step, the resulted dichlorostilbene undergoes hydro-
genolysis followed by hydrogenation to bibenzyl in the final step, which can
only occur in the presence of a hydrogen source such as formate salt. The
reaction is selective and catalytic in Pd catalyst. Therefore, this work will
certainly encourage chemists to eliminate toxic waste of excess metallic
reducing agents previously used for this type of reaction.

Benzylic Halides
2721
ACKNOWLEDGMENTS
We thank Marcela Haimberg and Michael Mogilnitsky from the MS labora-
tory at Makhteshim Chemical Works, Beer Sheva, for GCMS analysis and
interpretation of several products in this study, and Frank Ling of University
of California at Berkeley for editing this manuscript. The financial support
from the Ministry of Science, Culture and Sport of Israel is highly appreciated.
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