from R&D Innovator Volume 2, Number 8 August 1993
$2 Present, Research for War, and a Nobel Prize
Brown, a 1979 Nobel Prize winner in chemistry, is the R.B.
Wetherill Research Professor of Chemistry at Purdue University.
Although he officially retired in 1978 (at 66), he
continues to carry on research with approximately 16 postdoctorate
500th anniversary of the discovery of America by Christopher
Columbus was celebrated in 1992.
Obviously, no new physical continents remain to be
discovered, but many new continents of science await discovery by
the past 50 years, my students and I found and explored the Borane
Continent, a feat that led to the awarding of the Nobel Prize. Let me tell you how this continent of science was discovered
early education was erratic because my father died when I was 14
and I had to work to help support my mother and three sisters. For two years after high school, I tried to find a
reasonable job, but this was the Great Depression, so in 1932 I
enrolled in a small junior college.
Having been told that the field paid well, I opted for
electrical engineering. I had to take chemistry in the first year, and since it
fascinated me, I decided to ignore the money and became a
1933 the college itself became a victim of the Depression.
When it went out of business, I had nowhere to go.
The following year, I enrolled in a junior college that had
just been opened by the City of Chicago, and then won a
scholarship that permitted me to receive a bachelor's degree in
chemistry from the University of Chicago in 1936.
decided to do doctoral research on the hydrides of boron.
At that time, it was a highly exotic field, and I had no
idea it would lead to methods for cheaply and efficiently
producing pharmaceuticals and other valuable compounds.
decision for a thesis field, I admit in retrospect, was made as
much by economics as anything else.
Let me explain how one classmate influenced my decision. When I received the B.S. degree, my girlfriend, Sarah Baylen,
gave me a graduation present.
This book, Hydrides
of Boron and Silicon, piqued my interest.
why did Sarah select this book from the hundreds of chemistry
books at the UC bookstore? Not
having much money, she picked the cheapest chemistry book in the
store and paid $2.00 for it.
So here's one method for selecting a research field leading
to a Nobel Prize!
let me explain more about boron.
Compounds of carbon, the central element of the periodic
table, form the basis of life.
The simplest hydrogen-carbon compound, methane, has one
carbon atom joined to four hydrogen atoms.
the right of carbon is nitrogen; the simplest hydrogen-nitrogen
compound is NH3,
ammonia. Move left from carbon and you find boron; the simplest
hydrogen compound of boron is BH3,
borane. While methane
and ammonia are found in nature and used by the billions of pounds
each year as fuel and fertilizer, respectively, borane is not
found in nature--it is too reactive.
The interest in borane was largely theoretical.
It could be isolated only as the dimer, diborane, and there
was considerable speculation about the electronic structure
involved in the dimerization.
I began work, diborane could only be made in tiny quantities by
very difficult methods. I'd
guess that not more than a dozen chemists throughout the world had
ever made or done research with this rare material.
my thesis, I undertook to explore the reaction of diborane with
aldehydes and ketones. I
soon found that diborane would conveniently reduce these
compounds, but there was absolutely no interest in my finding.
How could organic chemists use diborane as a reagent if it
was so rare?
like to say that we had the good sense to search for a practical
synthesis of diborane, allowing organic chemists to use our
process to reduce aldehydes and ketones.
But we didn't have enough good sense; what we had were the
imperatives of war research.
with my Ph.D. and allied with Sarah, who was now my wife, I looked
for an industrial job. But
I could not persuade anyone to hire me, and just when I thought I
was facing catastrophe, I was offered a postdoctorate at the
University of Chicago.
Keeping Up with War Needs
government wanted to find volatile, noncorrosive
compounds of uranium, without the corrosive properties of uranium
we were not informed of the objective, I know now that we were
working for the atom bomb project.
We used diborane to synthesize uranium borohydride.
As it fit the criteria, we were asked to make a large
quantity for testing.
this time, World War II had begun, and it soon became apparent
that, even with six people operating six diborane generators, we
would not be able to supply sufficient diborane.
We had to find a more practical route.
first attempt, the reaction of lithium hydride with boron
trifluoride, produced plenty of diborane.
When we happily reported our success to the government,
they told us lithium hydride was urgently needed for the war; none
could be spared for us. Someone
suggested that we use sodium hydride, but it would not react with
we discovered that methyl borate would react with sodium hydride
to form a new compound, sodium trimethoxyborohydride, which would
do everything lithium hydride would.
In particular, it would react with boron trifluoride to
produce diborane. And diborane reacted to produce sodium borohydride, a new
compound of major importance.
ready to synthesize quantities of uranium borohydride, we learned
there was no further need for new
noncorrosive, volatile uranium compounds, as the difficult
handling of uranium hexafluoride had been mastered.
was 1943. The Signal
Corps told us about their problem in field-generating hydrogen. They thought that our new chemical, sodium borohydride, might
solve their problem. Although
we had never used it for hydrogen generation, we had no doubt it
would react with water to liberate hydrogen.
they asked for a demonstration, I placed the borohydride in a
flask and put the entire assembly behind an explosion screen since
I didn't know how violent the reaction might be.
Everyone watched from a safe distance while I cautiously
reached behind the screen and turned the stopcock to drip water
onto the borohydride.
borohydride dissolved and the solution sat there looking at me!
No explosion--and no hydrogen.
This was one of the great shocks of my life and was the way
we discovered that sodium borohydride possesses an unusual
stability in water.
least we disproved our prediction that hydrogen would be produced.
However, we persuaded the Signal Corps to support research
into improved preparations for sodium borohydride.
We discovered that at elevated temperature, sodium hydride
and methyl borate would react to produce a mixture of sodium
borohydride and sodium methoxide.
needed a solvent to separate the two products.
We tried using acetone to separate borohydride from other
reaction products, but the acetone was converted to isopropyl
alcohol--the borohydride added hydrogen atoms to the acetone.
Thus we discovered a major application of sodium
borohydride—to hydrogenate organic molecules. We
went on to discover suitable solvents and suitable catalysts for
Signal Corps was delighted with the project and proposed to have
the material made on a large scale by the Ethyl Corporation. But then a directive from Washington told us the end of the
war was in sight and no new war plants would be built.
the war, Metal Hydrides Co. (now Morton, International)
manufactured sodium borohydride; it is currently made by
essentially our process in the millions of pounds per year.
1947, I joined the Purdue faculty and returned to studying
borohydride chemistry. Esters
such as ethyl acetate and ethyl stearate took up two hydrogens
from borohydride, as expected.
We found that ethyl oleate took up 2.37 hydrogens, a minor
discrepancy we might have swept under the rug.
However we discovered that the hydrogens were going into
the carbon-carbon double bond in ethyl oleate.
This reaction, hydroboration, turned out to be quite
valuable since it provided a simple means for converting
unsaturated organic compounds into other products.
explored hydroboration systematically for 10 years, and friends
asked me why. It was
a clean reaction, they pointed out, but all it did was produce
organoboranes, on which little work had been performed since their
discovery in 1862. They
therefore concluded that organoboranes could be of little
bided our time, then turned to the chemistry of organoboranes.
There, we discovered an unimaginable gold mine, a series of
compounds that have done practically everything we have
"asked" them to do and that have become the most
versatile intermediates available to chemists.
We can now use them to convert olefins and other
unsaturated organic molecules into almost any known class of
organic compounds (alcohols, aldehydes, ketones, acids, amines,
they exhibited a most unusual feature:
retention of stereochemistry.
Let me explain. Unlike
biologically produced compounds, chemically synthesized carbon
compounds often exist as a mixture of stereoisomers--mirror images
comparable to right and left hands.
This is a problem in the manufacture of pharmaceuticals
because usually only one of a stereoisomer pair is active.
Boron chemistry, however, gives us a practical method for
making only one of the pair, promising to revolutionize the
economics of the pharmaceutical industry.
example, Prozac, an antidepressant, introduced by Eli Lilly
several years ago, is sold only as a mixture of the two
stereoisomers. Attempts to separate the mixture into the individual isomers
failed. But we found
it easy to synthesize the individual stereoisomers by our borane
route of "asymmetric synthesis."
Continents of Science to Discover
1936, when I received my bachelor's degree, I considered organic
chemistry a mature science, with essentially all important
reactions and structures nailed down.
The major challenges seemed to consist of working out the
reaction mechanisms and improving reaction yields.
I was wrong.
know many researchers today feel as I did back then. But I see no reason to believe that the next 56 years will be
any less fruitful than the past 56.
We're still naming the new continents of science!