Johann Friedrich Wilhelm Adolf von Baeyer

34 Pages·2014·0.27 MB·English

GENERAL(cid:168) ARTICLE
Johann Friedrich WilhelmAdolf von Baeyer
A Pioneer of Synthetic Organic Chemistry
GopalpurNagendrappa
Important discoveries inchemistry most certainly contribute
to the industrial and economic developments and indirectly
direct the course of history. A majority ofBaeyer’s research
findings are of this kind. In the pursuit of synthesising a
variety of organic compounds for more than half a century,
Baeyer became the first chemist who can be considered as
GNagendrappa was a
classical synthetic organic chemist. He did groundbreaking ProfessorofOrganic
researchin sixteendifferent areas of organic chemistry, such ChemistryatBangalore
University,andHeadof
asdyes, hydroaromaticcompounds, polyacetylenes,uric acid
theDepartmentof
and related compounds, natural products. Baeyer’s strain
MedicinalChemistry,Sri
theory is acommontextbooktopic at the UGlevel. His work Ramachandra (Medical)
on hydroaromatic compounds strongly supported Kekule’s University,Chennai.Heis
currentlyinJainUniver-
benzene structure. For this and the work on dyes, he was
sity, Bangalore. He
awarded the 1905 Nobel Prize in Chemistry.
continuestoteachanddo
research.Hisworkisin
Introduction
theareaoforganosilicon
chemistry, synthetic and
Organic synthesis is the science as well as the art of putting
mechanistic organic
togethersimplermoleculesstep-by-stepinordertogetamolecule chemistry,and clay-
ofpreviouslydeterminedmorecomplexstructure.Themethodol- catalysed organic reactions
(Green Chemistry).
ogy had a humble beginning around the mid-nineteenth century
and has reached a stage where it has become possible to make
molecules of mind-boggling complexity.
Starting with alizarine and then indigo, the two important dyes
that used to be extracted from plant sources, Baeyer and his
associateswereabletofirstsystematicallydeterminetheir struc-
tures and synthesise them by rationally planned multistep reac-
tions.Themethodologytheyusedmayseemtobeprimitivenow,
but that was a great achievement then, and the fundamental
Keywords
principleof themethod is followed even today. During its initial Baeyer, dyes, alizarin, indigo,
period,organicsynthetic chemistrywas significantlyenrichedby straintheory,benzenestructure,
phthalein dyes, acetylenes.
the pioneering and multifaceted activity of Baeyer’s school,
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Evenasaboy whichnourishednotonlygoodchemistrybutgreatchemists, who
Baeyerhadakeen contributed immensely to the advancement of organic chemistry
interestinchemistry. subsequently. Here is a very brief account of Baeyer’s life and
Attheageoftwelve some of his achievements.
yearshediscovereda
Early Life and Education
doublesaltofcopper
whichwasfoundtobe
AdolfBaeyer wasborninBerlinonOctober 31,1835,toJohann
CuNa (CO ) .3H O.
Jacob Baeyer and Eugenie Hitzig, both of whom belonged to
2 3 2 2
highly respected and well-known families. Johann Jacob Baeyer
servedaslieutenant-generalinthePrussianarmyandalsotaught
in the army school. He was a famous geodesist who started the
European system of geodetic measurement and became the Di-
rector of Berlin Geodetical Institute. Eugenie’s father, Julius
EduardHitzig,wasajuristanddistinguishedhimselfinliterature
too. Hitzigs were Jews, but Eugenie converted to Evangelical
Christianity. (However, Jewish records show that Adolf von
Baeyer was the first Jew to get the Nobel Prize). Adolf was the
fourth of the five children of Johann Jacob and Eugenie Baeyer.
TheoldersiblingswereClara,EmmaandEduard,andtheyounger
was Jeanette, born respectivelyin1826, 1831, 1832 and1839.
Adolf completed his school education at Friedrich Wilhelm
GymnasiuminBerlin, andthenjoinedtheUniversityofBerlinin
1853.Evenasaboyhehadakeeninterestinchemistry.Attheage
of twelveyears he discovereda double salt of copper which was
found to be CuNa (CO ) .3H O. His fascination for the blue
2 3 2 2
indigowas somuch that hebought a lump of thebrilliant dyeto
celebrate his 13th birthday. However, when he joined Berlin
University he took physics and mathematics as subjects of his
Baeyer’s study. After three semesters at the university he had to go for
fascinationforthe compulsory military service in the Prussian army for a year.
blueindigowasso When he returned to his studies in1856 he went back to his old
muchthathe love, chemistry, and headed to Heidelberg to train under Robert
boughtalumpof Bunsen. After one semester, he worked there in the private
thebrilliantdyeto laboratory of August Kekule. While in Heidelberg with Bunsen
celebratehis13th and Kekule, he did his thesis work on methyl chloride and its
birthday. arsenicalor cacodylcompounds (e.g., Me As-AsMe ). Basedon
2 2
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this work, written in Latin, Baeyer was awarded the doctorate
degreein1858bytheUniversityofBerlin.Sincehedidnotgetan
academic appointment soon after, Bayer followed Kekule to the
UniversityofGhentinBelgium,wherethelatterwasappointedas
Professor inthesameyear.AtGhent,Baeyerstartedhisworkon
finding the constitution of uric acid (Box 1).
Box 1.
Uricacidhasalonghistory.ItwasdiscoveredbyKarlWilhelmScheelein1776inbladderstoneandhuman
urine. He studied some of its properties. It is a major constituent of excrement of birds and reptiles, but
mammals excrete it rarely. Though healthyhuman urine has hardly anyof this substance, gout patients’
urinecontainsitinsignificantamounts.Itformsinthebodyasametabolicproductofproteinsandpurines
in nucleic acids. Because of its importance in animals and humans, a lot of work has been done on its
chemical, physiological, pathological and other biological aspects.
From Scheele to Friedrich Wöhler and Justus von Liebig many chemists studied its properties and
reactions.LiebigandMitscherlich independentlydetermineditsmolecular formulaas C H N O in 1834.
5 4 4 3
Between 1834 and 1838, theysubjected uric acid to manyreactions.
Baeyer’sworkonuricacidandrelatedcompounds–pseudouricacid, hyeluricacid,violuricacid,dilituric
acid and their salts, violautin (a complex derivative of barbituric acid), and allaxan bromide, allaxan
derivatives, nitromalonic acid, mesooxalicacid and some of their derivatives – duringthe first half of the
1860sgavesomecluetoitsconstitution.Severalstructureswereproposedforuricacidin1870s(soonafter
Kekule’s structural theory was proposed). The structure proposed byL Medicus in 1875 was confirmed
by E Fischer in1882.
O O
HN CO HN CO
CO C NH.CN CO C HN HON NH HN NH
H CO
HN CO HN C NH O N O O O
H
Baeyer1863 Medicus1875 O
Uricacid Violuricacid Allaxan
O
C
HN NH2 NO2
O O O O
HN NH HN NH NO2 O
O O HO2C CO2H HO2C CO2H
Pseudouricacid Dilituricacid Nitromalonicacid Mesoxalicacid
(5-Ureidobarbituricacid) (5-Nitrobarbituricacid)
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Baeyerusedthe BacktoBerlin–aLongTeachingandResearchCareerStarts
structuraltheoryin
Baeyer presentedhisuric acidworkat Berlin Universityin 1860
hisresearchtosolve
by which he earned the eligibility to teach there. As a result,
themolecular
BerlinUniversityappointedhimasa PrivatDozent(similartoan
structuresandlater
assistant professor) at a constituent institution, the Gewerbe
providedsolid
Akademie1.TheAkademieprovidedBaeyera biglaboratory, but
experimentalsupport
he was given very little remuneration and inadequate funds for
tothetheory,
thelaboratory.However,hewasquitehappytobeintheAkademie,
particularlyto
becauseatthattimetheUniversityofBerlindidnothaveaproper
Kekule’sbenzene
chemical laboratory.
structure.
Baeyer’s association with Kekule had greatly benefited him in
terms of getting to know firsthand the latter’s ideas on the
structuraltheoryfromits initialstage. Baeyer usedthestructural
1Trade Academy or the Berlin
theoryin his research to solve themolecular structures and later
College of Vocational Studies,
which was later renamed as providedsolidexperimentalsupporttothetheory,particularlyto
Charlottenburg Technische Kekule’s benzene structure. Though Kekule was older and
Hochshcule, and now has be-
Baeyer’s doctoral thesis adviser, the two had a very cordial and
come the Technical University
friendly relationship throughout their lifetime.
of Berlin
In Gewerbe Akademie, Baeyer continued to work on the prob-
lems he was engaged in earlier. The experience he had gained
fromthestudies onuric acidenabledhimin1864 to develop the
Box 2.
Barbituric acid is the parent compound of a class of more than 2000 medicinal compounds called
‘barbiturates’. The first barbiturate of medicinal application was ‘barbital’ synthesised by Emil Fischer
andvonMering.Itisalong-actingsedative.Itwastestedonadog,whichsleptpeacefullyformanyhours.
Itwasmarketedunderthename‘Veronal’,namedbyvonMeringafterthecityofVeronainItaly,because
he considered it as the most peaceful place in the world.
O O
O EtO OEt HN NH HN NH
+
H2N NH2 O O O O O O
Urea Malonicester Barbituricacid CH CH
2 5 2 5
Barbitalor
Veronal
Box2.continued
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Box2.continued
Asfortheoriginofthename‘barbituricacid’,therearemanystories.Butthemostcredibleoneseemsto
bethefollowing.Thedayon which the compoundwaspreparedhappenedtobeSaintBarbaraFeastDay.
Baeyer was celebratinghis discoveryof the new compoundin a pub, where a guest suggested to him to
use the name of the saint. Thus combining Barbara with urea, Baeyer coined the word ‘barbituric’ and
ended it with ‘acid’.
There are other interesting stories, which are most likely made up. One such is this. At the time when
Baeyersynthesisedbarbituricacid,hehadagirlfriendnamedBarbaraafterwhomhenamedthecompound.
Yetanother,quiteaqueerone,isthat theureausedforthesynthesisofthecompoundwas extractedfrom
the urine of a local bar maid named Barbara.
synthesis of barbituric acid (Box 2) by condensing diethyl
malonatewithurea(Scheme1).(Itshouldberememberedthatthe
structures written here were unknown in this formthen.) By1869he
convertedindigo
In 1865, Baeyer started his life’s most important work, namely intoindolethrough
the determination of indigo structure (more about this later),
aseriesof
whichheld his attention for nearly two decades. Heproposed its reactions.Thus,
correctstructurefinallyin1883. Thereafter,hecontinuedtotake
hediscovered
interest in making its commercial production possible. indole,oneofthe
mostimportant
In 1866, impressed by the success of young Baeyer, August
heterocyclic
Wilhelm Hofmann, who was then Professor and Director of the
compounds.
chemistrylaboratory inBerlin University, recommended himfor
Professor’s position. Baeyer was promoted, but was not given
financialbenefits. ThoughBaeyer felt unhappy about this, it did
not detracthimfromhis hardwork. By1869heconvertedindigo
into indole through a series of reactions. Thus, he discovered
indole, one of the most important heterocyclic compounds.
In 1867, he took a leading role in establishing the Deutsche
O O
C2H5O OC2H5 H2N NH2
+ HN NH + 2C2H5OH
O O O
O
Diethylmalonate Urea Barbituric
Scheme1.Baeyer’sbarbitu-
acid
ric acid synthesis.
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Chemische Gesellschaft zu Berlin, the oldest forerunner of the
present day Gesellschaft Deutscher Chemiker (Society of Ger-
man Chemists). The first President of the Society was AW
Hofmann and the Secretary was Baeyer.
2 TheUniversity was named af- In1872,theUniversityofStrassburg2(StrasbourginFrench)was
ter the Prussian ruler Kaiser re-establishedunder Prussianrule after the Franco–German war
Wilhelm. It has a long history
of1870–71endedandStrassburgwascededtoGermany.Baeyer
starting from the 16th century
wasofferedthepositionofChairofOrganicChemistrythere,and
under German rule. It changed
hands several times between he gladly accepted it. There he continued to work on uric acid
FranceandGermany,andpres- derivatives,nitrosocompounds,indigo, andalsostartedresearch
ently it is the second largest
onphthaleindyesandphenol-formaldehydereactions.OttoFischer
university in France.
andEmilFischer3 joinedhimasPhD students. Baeyer stayedin
3 See Resonance, Vol.16,
Strassburg only for three years and moved to the University of
pp.606–618, 2011.
Munich in 1875 to succeed Justus von Liebig4, an eminent and
4 See Resonance, Vol.18, influential chemist, who had passed away in 1873. He was
pp.397–417, 2013.
associated withMunichUniversityfor thenext 43 years untilhe
retiredin1915at theageof80 years,just 2yearsbeforehedied
on August 20, 1917. During this period he completed his most
important work on the elucidation of the structure of indigo and
its synthesis, proposed the strain theory of ring compounds,
worked on the C- and N-nitroso compounds and acetylenes,
provided a great deal of experimental evidence for Kekule’s
benzene theory, discovered oxidation of ketones with peracids
(Baeyer–Villiger reaction), continued his collaboration with the
BASF chemicalcompany bywhich he greatly contributedto the
development of the German dye industry, and received, apart
fromother honours, the NobelPrize in1905.
Marriage and Family
Baeyer married Adelheid Bendemann in 1868. They had four
Baeyerwas children: Eugenie (Baeyer’s mother’s namesake), Franz, Hans
associatedwith Emil Ritter andOtto, bornrespectivelyin1869, 1870,1875 and
MunichUniversity 1877. Eugenie married the well-known organic chemist Oskar
forthenext43 Piloty.PilotyhadjoinedBaeyerforhisPhD,butlaterworkedand
yearsuntilhe obtained the degree under Emil Fischer at Berlin (Box 3). Franz
retired. died at the age of 10. Hans Emil Ritter von Baeyer studied
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Box 3.
Oskar Piloty (1866–1915) fell in love with Eugenie while working as a doctoral student of Baeyer. The
story is that as Baeyer did not like the affair, he failed Pilotyin an examination and Piloty had to leave.
However, Piloty joined Emil Fischer and obtained his PhD degree at the University of Würzburg and
married Eugenie. He moved to the University of Berlin with Fischer. In 1900, Baeyer offered Piloty a
position in his department in Munich, which Piloty accepted, although Fischer offered him a better
position in Berlin. Pilotyhadto gofor compulsorymilitaryservice duringWorld War I. He was killedin
1915 during a fight at the battle of Champagne in the Western Front. His research workwas in the field
of natural products, particularly on the structure of haemoglobin.
medicine and became Professor of Orthopaedics and Physician-
Bayerislistedasthe
in-Chief at the University of Heidelberg. In 1930, he was the
firstamongthe191
President of the German Society for Orthopaedics. In 1933, he
Jewswho havewon
was dismissed by the Nazi government, because of his Jewish
theNobelPrize,
ancestry.(AdolfvonBaeyer’smother as wellashiswifewereof
whichamountsto
Jewish descent and he is listed as the first among the 191 Jews
about22%ofall
who havewon the NobelPrize, whichamounts to about 22% of
NobelPrizewinners
allNobelPrizewinnersworldwidebetween1901and2013,while
worldwidebetween
theJewsconstitutejustabout0.2%oftheworldpopulation).Otto
1901and2013,
von Baeyer became Professor of Physics at the Agricultural
University in Berlin.
Awards and Honours
The impact of Baeyer’sworkindifferentareas oforganic chem-
istry on contemporary and later research and German chemical
industry was enormous. The methodology he developed for de-
termining the structures of a large number of organic molecules
was highly systematic, and the crowning glory was solving the Theimpactof
structureandthesynthesis oftheso-called‘kingofdyes’,indigo, Baeyer’sworkin
(whichwasconsideredatthattimeasa toughtask)accomplished differentareasof
with great skill, perseverance and hard work. It was the first organicchemistryon
natural product molecule whose structure was solved systemati- contemporaryand
callybydegradativereactionsfollowedbyanalysingtheproducts laterresearchand
formed, which culminated in developing several logical routes by Germanchemical
himandothers for itssynthesis.Theprocedurebecamea modelfor industrywas
natural products studies. The development of industrial production enormous.
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Indigohadaspecial of syntheticindigo hada specialimplicationfor Indianagriculture,
implicationforIndian andtheeconomic,socialandpoliticalsettingintheearlypartofthe
agriculture,andthe 20thcentury5.
economic,socialand
These accomplishments naturally attracted recognition by the
politicalsettinginthe
academic, scientific and industrial community and Baeyer was
earlypartofthe20th
honouredwithawards,prizesandinotherways.In1905,hewas
century.
given the Nobel Prize “in recognition of his service in the
advancement of organic chemistry and the chemical industry,
throughhisworkonorganicdyesandhydroaromaticcompounds”.
5See Resonance, Vol.8, No.3,
pp.42–48, 2003. The accolades had started pouringin much earlier. In 1881, the
Royal Society of London honoured him with the prestigious
Davy Medal. In 1884, he was elected foreign honorary member
of the American Academy of Arts and Sciences. On his 50th
birthday(in1885)Bayer, likehispredecessor Justus vonLiebig,
wasbestowedwiththestatusofhereditarynobilitybytheBavar-
ianruler,andsincethenhisfamilynamegottheprefixofhonour
‘von’. In 1891, the Bavarian government conferred himwith its
highestcivilianaward‘OrderofMaximilian’. Likewise,in1894,
thePrussiangovernmentgranted‘OrderpourleMerite’. Baeyer’s
studentscelebratedhis70thbirthdayandtheoccasionwas com-
memorated by the publication of two volumes of Collected
Works(GesemmellteWerke),a collectionof hisresearchpapers
classified in sixteen groups (more on this later). On his 75th
birthday, an endowment was created in his honour by Carl
6One of the giant chemical in- Duisberg, who, once Baeyer’s assistant in Munich, became one
dustries of Germany,BayerAG, of theoutstanding industrialchemists of the20thcentury6. With
thrived under Duisburg’s leader-
theproceedsofthisendowment,theSocietyofGermanChemists
ship
presents the Adolf von Baeyer Medal once in 2–3 years to a
distinguished organic chemist.
Baeyer’s Scientific Achievements
Baeyer’sresearch Baeyer’s research activity spanned almost sixty years of the
activityspanned eighty-two years of his life, though the last ten years were not
almostsixtyyears quite productive, as he published only two of his 305 papers in
oftheeighty-two thisperiod.Therangeoftopicsheworkedonisamazinglyvaried
yearsofhislife. and spread over many different classes of organic compounds.
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ThetwovolumesoftheCollectedWorksbroughtoutathis70th
birthday celebrations together consisted of sixteen different
areasof research:(1) Organicarsenic compounds,(2) Uric acid
group, (3) Indigo – indigo researches, (4) Pyrrole and pyrrole
bases, (5) Condensation reactions, (6) Phthaleins, (7)
Hydroaromatic compoundsandstructureof benzene,(8) Terpe-
nes, (9)Nitrosocompounds, (10)Furfural, (11) Acetylenecom-
pounds and strain, (12) Peroxides, (13) Basic properties of
oxygen and oxonium salts, (14) Dibenzalacetone and triphenyl-
methane,(15)Aromaticseries,and(16)Aliphaticseries.Mostof
themwereof fundamentalimportanceinadvancing theprogress
of organic chemistry. Althougheachoneof thesetopics became
significant,theonesthatmadethegreatestimpactonthecontem-
porarychemistryincludeindigo, hydroaroamtic compounds and
strain theory of ring compounds.
Before Baeyer started his work on indigo, his major research
activityduring1860–1865wasintheareaofuricacidandrelated
compounds. Theanalysis of the components and characteristics
of urinehadengagedthe attentionofscientists andmedical men
sincea longtime. Fromthetime Walter Scheeleisolatedit from
kidneystones,manyleadingchemistsworkedonvariousaspects
ofitsproperties,reactionsandstructure.(MoreonthisinBox1.)
WorkonDyes
Baeyer’s research work on indigo has special significance to
India, because the synthetic indigo completely eliminated the Thesordidevents
cultivation of indigo plants which had provided livelihood to a broughtMahatma
large number of farmers, labourers and traders. The shift from Gandhi onthescene
natural to the synthetic dye brought misery not only to these toresolvethrough
communities, but it also led to a minor social and political negotiationsthe
upheavalin a largepart of Bihar andBengalin theearlypartof conflictthathad
the20thcentury.ThesordideventsbroughtMahatmaGandhion ensuedbetweenthe
the scene to resolve through negotiations the conflict that had farmersandthe
ensued between the farmers and the landlords who had leased landlordswhohad
land to cultivate indigo crop. Gandhiji’s intervention was ini- leasedlandtocultivate
tially prevented by the British rulers, but they quickly relented indigocrop.
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Indigocharacterises when they realised that they could not handle the consequences
themagnificenceof ofthefirmstandhehadtakentoresolvetheissue.Itwasthefirst
AdolfvonBaeyer’s instance of the Mahatma’s involvement with the civil disobedi-
researchworkandis enceaspart oftheIndianindependencemovement. Moreonthis
integraltothestoryof subject and chemistry aspect can be found inearlier Resonance
hislife. articles7. Synthetic indigo had impact on commercial interests,
history and of course chemistry. It characterises the magnifi-
cenceofAdolfvonBaeyer’sresearchworkandisintegraltothe
story of his life. Therefore, a perspective of indigo chemistry is
7 See Resonance, Vol.16,
presented here.
pp.1168–1175, 2011; Vol.17,
pp.1022–1033, 2012.
Alizarin
Baeyerstartedhisresearchonindigoin1865.Theblue-coloured
indigo and the red-coloured alizarin were then the two most
important dyes in use; these were isolated from plant sources.
Indigo was produced mainly from Indigofera tinctoria and a
relatively small quantity from Isatis tinctoria (woad plant) in
Europe. Alizarin was extracted from the roots of madder plant
(Rubia tinctorum, the common madder; Rubia peregrine, the
In1868,Baeyer’s
wildmadder;andRubiacordifolia,theIndianmadder,Manjistha,
groupreducedalizarin
used even at the time of Mohenjo-daro). The common madder
toanthracenebyits
wasthemainsourceofalizarinandwasgrownlargelyinFrance.
drydistillationwithzinc
Carl Liebermann, who had obtained his PhD in 1865 under
dust,aprocedure
Baeyer,andCarlGräbe,whohadreceivedhisPhDfromHeidel-
discoveredbyBaeyer
bergunderthesupervisionofBunsen,wereinBaeyer’sgroup.In
whilereducing
1868, they reduced alizarin to anthracene by its dry distillation
anthraquinoneto
with zinc dust (Scheme 2), a procedure discovered by Baeyer
anthracene.
while reducing anthraquinone to anthracene. It was an exciting
revelationtoknowthatthebeautifulreddyeisasimpledihydroxy
derivative of anthracene.
Scheme 2. Reduction of al-
The fledgling chemical company, Badische Anilin and Soda
izarin to anthracene.
Fabrik, saw the commercial possibility in it and supported the
Zn+ ZnO
C14H8O4 C14H10 + 4H2O Gräbe-Liebermann
Distil
Alizarin Anthracene
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