christian_scot (christian_scot) wrote,
christian_scot
christian_scot

Research with Dr. Cody

After speaking with several professors about their research, and attending several discussions where research opportunities were presented to undergraduates, I have decided to start research this quarter with my Organic Chemistry professor, Dr. Jeremy Cody.  Dr. Cody is a great guy, and he has agreed to help me start a new project that he currently does not have anyone working on.  This quarter he will teach me techniques and instrumentation, etc, and I will most likely run through one reaction.  Henceforth, in the second, and third quarters, we will be cooperating with a local pharmaceutical company, who will provide materials for our lab, to examine why an azido ( N3−) group attached to an arylboronic acid has a rare tendency to form a nitrille (-C≡N) group, a much less stable substituent.  Not much is known about this, and as far as we know, only a few teams around the world are presently working to discover its significance.  We currently only know of three publications in which this phenomenon is mentioned.  One of which, Azidosubstituted arylboronic acids: synthesis and
Suzuki–Miyaura cross-coupling reactions
by Sviridov et. al. states,

"For example, nitrile 16 was
obtained in a yield of 32% in a parallel experiment
involving boronic acid 9 and 4-bromoanisol, when all the
reagents were loaded simultaneously into the reaction vessel
(entry 6). In some other experiments, this phenomenon
could occur when the reaction mixture was accidently
exposed to air, or when less active and sterically hindered
hetaryl chlorides were used, that is, when the catalyst
system has been somewhat different. Palladium-catalysed
conversion of azidomethyl group into nitrile is not
unprecedented (Pd/C or Pd black), although rare, the
yields being generally modest. Detailed investigations
revealed that this reaction is balanced to 2/3 of nitrile and
1/3 of amine that may suggest red-ox disproportionation of
the azidomethyl moiety; the use of an oxidant, however, did
not allow raising the yield of the nitrile product."

The abstract from this article is the following (the last sentence being the focus of our experimentation):

"Abstract—Arylboronic acids having a remote azido group were prepared from the corresponding azidosubstituted aryl bromides via
lithiation and treatment with trialkyl borates. Preparative yields were achieved when the starting aryl bromides possessed ortho-alkoxy
groups, which would stabilize the intermediate aryllithium species. Conventional Suzuki cross-coupling of the arylboronic acids proceeded
generally well with retention of azido group; however, sometimes azidomethyl fragment underwent oxidative transformation into a nitrile."

Also important to mention is the introduction which helps to explain the significance of this research:

"1. Introduction
During the last decade the Suzuki–Miyaura cross-coupling
leading to biaryls has become a widely used technology in
target synthesis, and in particular, medicinal chemistry. In
the synthesis of complex molecules, the organoboron
component is usually less structurally complex than the
more complicated aryl halide, which is due to the difficulties
in preparing arylboronic acids bearing certain functional
groups. On the other hand, the employment of sophisticated
arylboronic acids will be useful for combinatorial
chemistry, that is, they may serve as multifunctional
templates for the preparation of a broad variety of related
compounds. The application of such arylboronic acids in
medicinal chemistry is not unprecedented.
The preparation of structurally diverse arylboronic acids
bearing functional groups of electrophilic type from the
corresponding aryl halides using organolithium protocol
remained limited until Li and Nelson proposed an improved
‘in situ quench’ procedure when n-butyllithium was added
to a mixture of aryl halide and triisopropyl borate. Using
this technique, arylboronic acids with nitrile, ester and nitro
groups, as well as certain hetarylboronic acids, were
prepared directly from the aryl/hetaryl halide precursors in
reasonable yields.
To the best of our knowledge, organoboronic acids bearing
an azido group are not documented in the literature. The
azido group is a well known precursor to various nitrogen
containing compounds. On the other hand, it is very
convenient from the point of view of multistep synthesis: it
may tolerate a variety of reagents and conditions, and its low
polarity does not bring complications to isolation and
purification."

And, that is all I know for now.  I will post more when I have more than literature to read from.  My first meeting with Dr. Cody is next Monday at 4:30pm to discuss the commencement of our research.

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References:

Sviridov, S. I., Vasil’ev, A. A., Sergovskaya, N. L., Chirskaya, M. V., & Shorshnev, S. V. (2006). Azidosubstituted arylboronic acids: synthesis and suzuki–miyaura cross-coupling reactions. Tetrahedron, (62), 2639–2647.
Tags: arylboronic acids, azide, azido, dr. cody, group, nitrille, palladium, research, synthesis
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