Hydrodehalogenation of Aromatic Halogens Using
Sodium Borohydride and Palladium under
Ambient Conditions
Zach M. Rousslang, Alyssa Russo and Dr. David B. Cordes
Department of CHEMISTRY | Pacific University | 2043 College Way | Forest Grove, OR 97116 | cordes@pacificu.edu
Abstract: Using sodium borohydride as the reducing agent and catalyzed by activated palladium on carbon, the reductive dehalogenation of aromatic halides is observed under room temperature and pressure.
This heterogeneous reaction mixture employs isopropyl alcohol as the solvent and provides high conversion yields within an hour reaction time. The effects of the local electronic environment on yields are
currently being studied using halogenated benzonitriles, toluenes, anisoles, and benzenes.
BACKGROUND:
The reductive hydrogenation of organic molecules is a cornerstone of synthetic chemistry. This tool allows
chemists to manipulate the polarity, reactivity, and overall composition/structure of unsaturated hydrocarbons.
Since its advent, hydrogenation has developed niches in many fields such as material science, natural products
research, and in both food and medicinal chemistry. Due to the ubiquitous importance of unsaturated
hydrocarbons many methods have been developed for their reduction. Some of the existing methodologies
require expensive reagents, complex multiphase systems, and produce harmful byproducts
RESULTS:
Selective Reduction of α-β Unsaturated Compounds:
NaBH4 (4 equiv), CH3COOH (2 equiv)
2.5% Pd/C
R
R
Toluene or IPA, 1.5 hour, open air
Halogens are one of the most reactive chemical families due to their high nuclear charge. Their reactivity and
polar nature are of critical importance for many biological and chemical processes, yet they can also be
extremely toxic in the wrong environment. Aromatic compounds are notorious for electron delocalization and
thus these conjugated systems are susceptible to halogen interaction. The stabilizing effects of this interaction
can produce highly inert compounds, which can pose a problem for waste management. Hydrodehalogenation is
a sub-field of hydrogenation chemistry where a halogen is effectively replaced with hydrogen and has
significant applications in many of the same areas as basic hydrogenation.
Yield
Product
Substrate
NH2
NH2
O
O
98%
O
O
99%
N
N
O
O
BOROHYDRIDE REDUCTIONS:
99%
Borohydride reagents are ordinarily used for the reduction of polar functional groups, especially with
carbonyl-containing compounds such as ketones, aldehydes, and esters. Among the borohydride reagents,
sodium borohydride in particular is valued for its low cost, mild nature, and ease of handling. Surprisingly,
however, this green reagent has found only limited use in the reduction of less polar functional groups.
O
O
99%
Hydrodehalogenation of Aromatic Compounds:
The hydrolysis of borohydride produces hydrogen gas. In the presence of hydrogen gas, reduced metals
are found to catalyze the reduction of alkenes.
Simple Reductions Using Pd/C and NaBH4:
Initial research was conducted using our method for the hydrogenation of alkenes and alkynes. High
conversion yields have been obtained for many simple unsaturated hydrocarbon. A solvent study
indicated that isopropyl alcohol (IPA) was the most effective solvent.
ALKENE
or
ALKYNE
4 NaBH4, 2 CH3COOH,
catalytic Pd/C
IPA, RT, open air
ALKANE
90% or higher
conversion
Aromatic halogen
(1mmol)
Substrate
4 mmol NaBH4, 5 mL IPA
5% mol Pd/C, 1 hour, open air
Product
Yield
CN
CN
Cl
CN
Substrate
CN
Product
CN
93.3 %
CN
95.8 %
96.1 %
Br
Cl
CN
CN
Yield
CN
Br
57.2 %
CN
Hydrodehalogenated
aromatic
CN
CN
98.0 %
99.0 %
I
Br
Substrate
Product
Yield
Substrate
Product
F
Cl
Reactions occurred rapidly under ambient conditions.
Molar percent catalyst ranged from 1 to 5%.
Yield
7.4 %
1.6 %
16.1 %
3.1 %
F
Cl
OUR STANDARD PROCEDURE:
Current Procedure:
1. An air-dried round bottom flask with stir bar is charged in open air with the alkene, α-β unsaturated
compounds, or aromatic halogen, (1 mmol), 5 mol % Pd/C, and 5 mL isopropyl alcohol (IPA) .
2. Solid NaBH4 (4 mmol) is added in a single portion directly to the stirring heterogeneous solution. (Note:
Addition of the NaBH4 causes the rapid evolution of small hydrogen gas bubbles.)
3. The contents of the reaction flask are left to stir in open air at room temperature.
4. Workup is conducted by quenching the reaction mixture or reaction aliquot with 0.1 M HCl until no
further hydrogen evolution is observed. The solution is then made basic with saturated NaHCO3. The
products are then extracted from the basic solution with ether, dried over anhydrous MgSO4 and
filtered. The solvent can be removed by evaporation at reduced pressure.
5. Reactions are typically analyzed by GC/MS.
11.9 %
3.7 %
F
Cl
Substrate
OCH3
Cl
Product
Yield
OCH3
99.8 %
OCH3
OCH3
Substrate
Product
OCH3
Br
OCH3
OCH3
OCH3
94.9 %
87.2 %
99.9 %
Br
Cl
OCH3
OCH3
OCH3
OCH3
99.9 %
Cl
Yield
99.9 %
Br
FUTURE DIRECTIONS:
Acknowledgements: Pacific University and the Department of Chemistry;
The Murdock Charitable Trust; Vincent Huynh and Anthony Tran
-Conclude systematic survey of reduction in simple aromatic halides.
-Perform mechanistic studies to develop probable reaction scheme.
-Fully optimize a method using water as the solvent.
-Devise methods for the isolation, purification and yield calculation of select halogenated aromatics.