THE DISCOVERY OF NEW CONTINENTS OF CHEMISTRY

HERBERT C. BROWN

1393 H. C. Brown and R. B. Wetherill Laboratories of Chemistry

Purdue University, West Lafayette, IN  47907 U.S.A.

          The 500th Anniversary of the discovery of America by Christopher Columbus was celebrated in 1992.  The geography of the planet Earth is now sufficiently well known to make it clear that there remain no new physical continents to be discovered, but there are many new Continents of Science awaiting discovery and exploration by energetic and enthusiastic explorers.  In the past sixty years, my students and I have discovered and explored such a new continent, the Borane Continent, a discovery which led to the awarding of the Nobel Prize in Chemistry in 1979 to me and to Purdue.  I believe that a brief review of how this new Continent of Science was discovered and explored as part of the teaching and research function of a modern university will make it clear why both activities - teaching and research - are essential to the operation of such universities.

 I.  BEGINNINGS

          My Father died when I was 14.  Consequently, my early education in high school was rather erratic as I worked to help support my Mother and three sisters.  I graduated high school in 1930.

          But life was very hard for young people in the Depression.  For two years I tried to find a reasonable job, without success.  In 1932, I decided to go to college and entered Crane Junior College in Chicago, the only college in the city of Chicago with no tuition.  I enrolled in the electrical engineering curriculum since someone had told me that electrical engineers received good salaries.

          However, as an electrical engineering student, I had to take chemistry the first year.  This subject fascinated me.  I decided to ignore the money and I transferred to chemistry.

          Crane closed its doors in June 1933, a victim of the Depression.  We had nowhere to go.  fortunately, one of the teachers, Dr. Nicholas Cheronis, had a small laboratory in his backyard, a converted garage.  He invited several students to come there and do research, merely to give us something to do.  There I met a fellow student, Sarah Baylen, who was to play a most important part in my life.

          The following year, the City of Chicago opened three junior colleges and Sarah and I went to Wright Junior College, with Nicholas Cheronis in charge of chemistry.  We graduated in 1935, two of a total of nine graduates.

          I was fortunate enough to win a scholarship to the University of Chicago and entered there in the Fall of 1935.  At that time, the President, Robert Maynard Hutchins, was urging students to proceed as rapidly as they could.  It cost no more money to take ten courses per quarter than the usual three.  I could not resist the bargain and was scheduled to graduate in 1936.  It was my intention to graduate, get a job, and marry my classmate, Sarah Baylen.

          At this point, Fate, in the guise of Professor Julius Stieglitz, took a hand.  He was a renowned organic chemist, Past President of The American Chemical Society, and Professor Emeritus of the Department.  He asked me why I had not applied for a teaching assistantship, which would permit me to go on for a Ph.D.  I explained that I wished to marry my classmate and I did not see how I could manage both a marriage and a Ph.D. program.  He urged me to defer the marriage and to continue study toward the Ph.D.  After discussion with Sarah, she decided we should adopt his advice.

          I received a teaching assistantship.  It should not be thought that this made things very easy.  I was paid $400 per year for my half-time teaching appointment.  Out of this, I had to pay tuition, $100/quarter for three quarters.  In addition, I had to pay for my research expenses.  Things are a lot easier today.

II.  DOCTORATE

         I decided to do my doctorate research on the hydrides of boron.  At that time, this was a highly exotic field.

          The central element of the Periodic Table is carbon and carbon compounds provide the basis for life.  The simplest hydrogen compound of carbon is CH4, a carbon atom joined to four hydrogen atoms.  This is methane, otherwise known as natural gas.

          The element to the right of carbon is nitrogen.  The simplest hydrogen compound of nitrogen is NH3.  This is ammonia.

          The element to the left of carbon is boron.  The simplest hydrogen compound of boron is BH3, a boron atom joined to three hydrogen atoms.  This is borane.

          Whereas methane and ammonia are found in nature and are used in billions of pounds per year as fuel and as fertilizer respectively, borane is not found in nature.  It is too reactive, reacting rapidly with both water and oxygen.  At the time, it could be made in very small quantities by very difficult methods in only two places in the entire world: the laboratory of Professor Alfred Stock of Karlsruhe, Germany, and that of Professor H. I. Schlesinger of the University of Chicago.  Possibly not more than a dozen chemists throughout the world had ever made or done research with this rare material.

          The chief interest in these compounds was a theoretical one:  the true electronic structure.

          Why did I decide to do my research in this exotic area of boranes?  I owe this to my classmate, Sarah Baylen.  When I graduated with the B.Sc. degree in 1936, she presented me with a graduation gift, a copy of the book by Alfred Stock, Hydrides of Boron and Silicon.  I read this book, became interested in the subject, and decided to do my doctorate research in this area.

          But why did Sarah select this particular book out of the hundreds of chemistry books available in the University of Chicago bookstore?  This was the time of the Depression.  None of us had much money.  It appears that she selected as her gift the cheapest chemistry book ($2.00) in the bookstore.  This then is one of the ways to select a rich new research area that can lead to the Nobel.

          It was suggested by Professor Schlesinger and his Research Assistant, Anton B. Burg, that I explore the reaction of diborane with aldehydes, ketones and esters.  It was soon established that this was a general reaction, providing a convenient means for the reduction of such compounds.  My thesis, begun in 1936, was completed in 1938.  The research was published in 1939.

          There was absolutely no interest in this development.  We received no requests for reprints.  Why not?  At that time, diborane was a very rare substance.  It could be made in gram quantities in only two laboratories in the entire world.  How could organic chemists use diborane as a reagent when it was such a rare material?

          It would be nice to report to you that I or one of my two coworkers had the good sense to recognize the desirability of developing a practical synthesis of diborane.  Then all organic chemists throughout the world could use our process to hydrogenate aldehydes and ketones.  They would refer to our publication and we would become famous.  But we did not.  We achieved this later on, forced to do so by the requirements of war research, not because we had the good sense to recognize a major research opportunity.

III. POSTDOCTORATE INTERLUDE

            I now had my Ph.D. and a wife (Sarah), but no job.  I heard of an opening at the Sherwin-Williams Paint Company, but did not persuade them they needed me.  Another interview with the Patent Department of Universal Oil Products was not fruitful.  I thought I faced a catastrophe.  Just when things looked bleakest, Professor Morris Kharasch of the University of Chicago offered me a postdoctorate.

IV.  VOLATILE COMPOUNDS OF URANIUM

            The next year, 1939, Anton B. Burg left for the University of Southern California and Professor Schlesinger asked me to become his research assistant with the rank of Instructor.  I accepted.  Many individuals have ended up in industrial work because they could not find academic positions.  I am an unusual example of an individual who ended up in academic work simply because he could not find an industrial position.

          Late in 1940, Professor Schlesinger was requested by the National Defense Research Committee to undertake a study of new volatile compounds of uranium.  It was necessary for the material to be non-corrosive¾unlike uranium hexafluoride¾, to be volatile, and to be of low molecular weight.

          Prior to this time, R. T. Sanderson had synthesized aluminum borohydride, bp 45°, and Anton B. Burg had synthesized beryllium borohydride, sp 91°.  These are the most volatile aluminum and beryllium compounds known.  Accordingly, one approach we took was the synthesis of uranium borohydride.  We were successful.  It was non-corrosive and had a low molecular weight (298).  There was considerable interest in this material. We were requested to enlarge our group and to make a large quantity for testing.

V.  THE ALKALI METAL HYDRIDE ROUTE TO DIBORANE

            By this time, the attack on Pearl Harbor had occurred and we were in World War II.  It soon became apparent that the preparation of diborane was a serious bottleneck.  We had six young men operating six diborane generators.  When all went well, each generator could produce in eight hours 0.5 g of diborane, a total production per day of 3 g, ~1 kg/year.  Clearly, the War would be over, one way or the other, long before we could provide uranium borohydride in the quantity desired.  We were forced to find a more practical route.

          The first reaction we tried worked like a charm.  The reaction of lithium hydride with boron trifluoride produced diborane in quantity.  We happily reported this to Washington, but were informed we could not use lithium hydride.  All available lithium hydride was needed for other urgent war purposes.

          We tried to use sodium hydride.  It would not work.  However, we discovered that methyl borate would react with sodium hydride to form a new compound, sodium trimethoxyborohydride.  This compound would do everything that lithium hydride could do.  We were now in position to synthesize uranium borohydride in quantity.

          However, we now learned that the problem of handling uranium hexafluoride had been solved¾there was no longer any need for other volatile compounds of uranium.

VI.  PROCESS FOR SODIUM BOROHYDRIDE

            At this point (1943), the Army Signal Corps visited us.  They informed us that they had a problem with the field generation of hydrogen.  They thought that our new chemical, sodium borohydride, might solve their problem.

          We pointed out that on a weight basis, sodium borohydride should be far more efficient than their present chemicals, sodium hydroxide and ferrosilicon.  Although we had never used it for hydrogen generation, we had no doubt that it would be similar to diborane and other boron-hydrogen compounds in reacting readily with water to liberate hydrogen.

          They asked for a demonstration.  I placed a weighed quantity of sodium borohydride in a flask and attached it to a gas meter.  Above the flask therewas a dropping funnel containing water. The entire assembly was placed behind an explosion screen, since I did not know how violent the reaction might be.

          With Professor Schlesinger and all of the representatives watching me from a safe distance, I cautiously reached behind the screen and turned the stopcock to allow water to flow onto the borohydride.

          The borohydride dissolved and the solution sat there looking at me!

          This was one of the great shocks of my life and was the way we discovered that sodium borohydride possesses an unusual stability (for a simple boron-hydrogen compound) in water.

          Fortunately, the Signal Corps was persuaded to support research to find improved methods for preparing sodium borohydride and catalysts to facilitate its solvolysis.  We soon discovered that the addition of methyl borate to stirred sodium hydride at 250°C formed a mixture of sodium borohydride and sodium methoxide quantitatively.

          We required a selective solvent to separate these two products.  One solvent tested was acetone.  The borohydride dissolved: the methoxide did not.  Things looked good.  However, we could not recover the borohydride from the solution.  Hydrolysis gave four moles of isopropyl alcohol per mole of borohydride.

          In this way we discovered that sodium borohydride was a new valuable reagent for the hydrogenation of organic molecules.

          Liquid ammonia and isopropyl amine (more convenient) solved the separation problem.

          We also discovered that the addition of 3% cobalt chloride to pellets of sodium borohydride caused rapid hydrolysis.  The Signal Corps was delighted with the product and proposed to have the material made on a large scale by the Ethyl Corporation.  However, at that point, a directive was issued from Washington that the end of the war was in sight and no new war plants were to be built.

          After the war, Metal Hydrides undertook to manufacture this chemical by essentially our process and sodium borohydride is currently manufactured by this process in millions of pounds per year.

VIII.  SELECTIVE REDUCTIONS

            In 1947, Henry Hass Invited me to Purdue.  I decided to return to the study of borohydride chemistry and undertook a systematic study of hydride reducing agents.  At that time, two such reagents¾sodium borohydride and lithium aluminum hydride¾were known.  These represented two extremes: sodium borohydride, a very gentle reducing agent, and lithium aluminum hydride, a very powerful reducing agent.  I decided to search systematically for means of increasing the reducing power of sodium borohydride and of decreasing the reducing power of lithium aluminum hydride.

          We were successful in both endeavors.  In addition, we soon discovered major differences in the characteristics of “basic” reducing agents and “acidic” reducing agents.  In many cases, it became possible to reduce group A in the presence of B, or group B in the presence of A.

IX.  HYDROBORATION

            Perhaps the most valuable result of this systematic study of reducing agents was the discovery of hydroboration.  We were examining the reducing characteristics of sodium borohydride enhanced by aluminum chloride.  Esters, such as ethyl acetate and ethyl stearate, took up 2.0 hydride per mole of ester under our standard conditions (1 h at 25 °C).  However, ethyl oleate, an unsaturated ester, took up 2.37.

          We might easily have swept this little discrepancy under the rug. However, we did not.  We explored it.  We discovered that the carbon-carbon double bond in ethyl oleate was adding one molar equivalent of a hydrogen-boron bond from the reagent.

          Research soon established that diborane in ether solvents reacts readily with alkenes and alkynes to form organoboranes.

X.  ORGANOBORANES

            Hydroboration was discovered in 1956.  For ten years we explored the reaction systematically, until we felt we understood it satisfactorily.  A number of friends asked me why we were devoting so much effort to this reaction.  It was a clean reaction, they pointed out, but all it did was produce organoboranes.  Little work had been done on organoboranes since their discovery in 1862.  They therefore concluded that organoboranes could not be of much interest.

          We bided our time.  Then we turned our attention to the chemistry of organoboranes.  Here we discovered we had an unimaginably rich goldmine in our hands.  The organoboranes have done practically everything we have asked them to do.  They are presently the most versatile intermediates available to the chemist.  Moreover, they exhibit a most unusual feature, substitution with complete retention of stereochemistry.

XI.  THE BORON ROUTE TO ASYMMETRIC SYNTHESIS

            Compounds of carbon often exist as a pair of stereoisomers which differ only in the fact that they are mirror images, like our right and left hands.  Living organisms usually produce and use only one of a pair of such stereoisomers, but the classical synthetic methods usually produce only a 50:50 mixture of such stereoisomers, and it is both difficult and costly to separate them.  Boron chemistry, however, has now given us a practical method of making only one of a pair of stereoisomers.  This development promises to revolutionize the pharmaceutical industry in making it possible to prepare economically isomerically pure stereoisomers for medicinals, avoiding the common practice of manufacturing and selling 50:50 mixtures of such stereoisomers, only one of which is effective for the desired medicinal effect.

          Since organoboranes undergo substitution with complete retention of configuration, the development of a simple procedure for putting a single stereoisomeric group on boron should make possible a general method for achieving the simple synthesis of such stereoisomers.  Hydroboration with the simple borane derivatives of a a-pinene, a cheap terpene (from terpentine), made this possible.  We are now able to synthesize stereoisomerically pure compounds by simple, economic methods.

XII.  NEW CONTINENTS OF SCIENCE TO DISCOVER

          In this talk I have tried to transmit a number of lessons by describing my personal experiences over 60 years.  At the time I was a student in college, I had no inkling of what life would bring.  Developments that I thought were catastrophic at the time turned out well.  Life is a fascinating adventure.  We should not fear it

          Let me leave you with one last message.

          The research of my students and coworkers has taken this exotic group of chemicals¾diborane, borohydrides and organoboranes¾from unknown materials of little interest to important chemicals of major value as chemical reagents. We developed practical methods for their preparation and manufacture.  We discovered important new reactions of value to chemists interested in synthesizing complex organic structures.  some of our materials have solved major ecological problems.

          In 1936 when I received my B.Sc. degree, I felt that organic chemistry was a relatively mature science, with essentially all of the important reactions and structures known.  There appeared to be little new to be done except the working out of reaction mechanisms and the improvement of reaction yields.  I now recognize that I was wrong.  I have seen major new reactions discovered.  Numerous new reagents are available.  Many new structures are known.  We have at hand many new products and processes.

          I know that many of the students of today feel the way I did back in 1936.  But I see no reason for believing that the next 60 years will not be as fruitful as the past.

          In my book, Hydroboration, I quoted the poet:  “Tall oaks from little acorns grow.”  But in this lecture I have started further back, to a time when the acorn was a mere grain of pollen.  I have shown how that grain of pollen developed first into an acorn.  Then the acorn became an oak.  The oak tree became a forest.  Now we are beginning to see the outlines of a huge new Continent.

          We have been moving rapidly over that Continent, scouting out the major mountain ranges, river valleys, lakes and coasts.  But it is evident that we have only scratched the surface.  It will require another generation of chemists to settle that Continent and to utilize its riches for the good of mankind.

          But is there any reason to believe that this is the last new continent of its kind?  Surely not.  It is entirely possible that all around us lie similar Continents of Science awaiting discovery by enthusiastic, optimistic explorers.  I hope that one result of this lecture will be to inspire young chemists (and young people in all other areas of knowledge) to search for such new Continents.

          Let’s go forth to find them!  GOOD LUCK!