Synthetic Dyes
and
the Development of Organic Chemistry
O
NH2
N
H
OH
NH2
N
N
OH
N
H2N
NH2
O
alizarin
Bismarck brown
H
N
HO
N
MeO
H2 N
N
N
H
N
quinine
H2 N
NH2
mauveine
fuchsin
O
Me
General References:
NH2
H
N
+
N
H
Aftalion, F. A History of the International Chemical Industry. Philadelphia: University of Pennsylvania Press, 1991.
Beer, J. J. The Emergence of the German Dye Industry. Urbana, IL: Univeristy of Illinois Press, 1959.
O
indigo
Benfey, O. T. and P. J. T. Morris, eds. Robert Burns Woodward. Philadelphia: Chemical Heritage Foundation, 2001.
Christie, R. M. Colour Chemistry. Cambridge: Royal Society of Chemistry, 2001.
Gordon, P. F. and P. Gregory. Organic Chemistry in Colour. Berlin: Springer Verlag, 1983.
Honigsbaum, M. The Fever Trail: In search of the Cure for Malaria. New York: Farrar, Straus and Giroux, 2001.
Pratt, L. S. The Chemistry and Physics of Organic Pigments. New York: John Wiley and sons, Inc., 1947.
Stork, G.; Deqiang, N.; Fujimoto, A.; Koft, E. R.; Balkovec, J. M.; Tata, J. R.; Dake, G. R. J. Am. Chem. Soc. 2001, 123, 3239.
-----------------------------------------------------------------------------------------1856 – A synthetic route to quinine?
H
H
HO
N
MeO
N
quinine
Gradually came into use in mid-1600s
Isolated in 1820 – Pelletier and Caventou
Extracted from the bark of cinchona tree found in the Andes
By early 1800s, native sources almost exhausted
Prices soared despite cultivation elsewhere
Empirical formula established in 1854 – Adolph Strecker
1
1856 – Perkin's Easter vacation
Formula, but not structure of quinine known
Perkin attempted oxidation:
KCr2 O4
H2 SO4
2C10H13N + 3[O]
C20H24N2O2 + H2O
quinine
William Henry Perkin, age 14
H
H
HN
[O]
HO
N
MeO
N
Experiment resulted in v. impure brown powder, but Perkin tried to assess whether the oxidation
was general:
N
NH2
NH2
KCr2O 4
H2 SO4
EtOH, reflux
black sludge
H2 N
N
N
H
+
Me
impurities
purple crystals = "aniline purple," later mauveine
-------------------------------------------------------------------------------------------------------1857 – An industry began
Current synthetic dyes were unsuitable, but demand was high
OH
O2 N
NO 2
NO2
yellow
made from phenol
not lightfast
O
H O
N
O
HN
H
N
NH
N
O
O
O -NH4 +
reddish-purple
reasonably light-resistant
application complex and expensive
synthesize from urea and nitric acid
murexide
picric acid
Perkin left school, father risked fortune
Success required establishment of large scale organic chemicals industry
Raw materials to make aniline needed on large scale: benzene, nitric acid, aniline
Perkin's sketch of Perkin and Sons dye factory
2
1800-1845 – Coal tar and Justus Liebig set the stage
In late 1700s coal distilled for tar; after 1812, illuminating gas became desirable, excess coal tar
accumulated
Liebig one of the premier educators of all time
Fresenius, Erlenmeyer, Kekulé, Wurtz...
Small links between industry and chemistry established
August Wilhelm Hofmann began to analyze coal tar extracts
Hofmann establishes Royal College of Chemistry in England*
Liebig's lab in Giessen
----------------------------------------------------------------------------------------------------------H N
NH
1856-1867 – Post-mauveine developments
2
2
Concious search for new dyes – fuchsin found by Emanuel Verguin
Triphenylmethine dyes enable systematic synthesis of new compounds – Hofmann
NH2 +
rosaniline or fuchsin
Production of mauveine stopped after ten years
1867 – value of dyes had tripled since 1862 despite price drops
N
NH2
Price per kilo of raw materials and dyes
aniline yellow
+
1862
1867
benzene
5 fr
70 c
rosaniline
300 fr
30 fr
N
HN
SO3 NH4
-
O3S
N
H
NH
SO3 NH4
aniline blue
N
N
N
N
N
OH
H
[O]
+
OH
N
N
N
malachite green
3
1858 – Peter Griess and the azo dyes
More Germans in England
NH2
N+
HNO 2
2
NH2
N
N
diazotization
N
azo coupling
NH2
aniline yellow
Peter Griess
Otto Witt, Heinrich Caro and Carl Alexander Martius
Versatile chemistry exploited
N
N
H2 N
Azo dyes today account for 60-70% of dyes used in textile applications
NH2
chrysoidine
N
O
Y
H2 +
O
N
N
-YNH2
O
N
O
HO
N
N
N
O
nitrosoacidium ion
nitrious acid
-
H
N
-H+
+
O
H2O
N
N
OH
N
H+
N
OH2 +
N+
-H2 O
N
nitrosonium cation
O
+
N
O
pH important in diazotization as
well as azo coupling
nitrite anion
O
N
O
N
Y
O
O
N
Cl
N
O
nitrosyl chloride
dinitrogen trioxide
increasing acidity
---------------------------------------------------------------------------------------------------------1869 – Alizarin, then decline for England and France
O
1868 – Graebe and Liebermann deduce structure
OH
OH
Perkin and Sons first commercial producers: 1869 - 1 ton
1870 - 40 tons
Class of carbonyl dyes – anthraquinones
1871 - 220 tons
O
alizarin
Madder
Graebe and Liebermann:
Caro, Perkin:
O
O
Br
O
O
O
Br
Br2
SO3 H
H2SO 4
O
O
O
NaOH, !
O
O
[O]
OH
Br
O
OH
SO3 H
O
SO 3H
OH
OH
Br
O
O
O
O
But England was on the decline:
France too:
Hofmann departs in 1865
Not enough trained chemists
Minimal state funding
Business complacency
Little cultivation of scientific inquiry
Not enough raw materials
Loss of Alsace-Lorraine in 1871
Patents for products, not processes
Private labs did not supply enough trained chemists
4
German industry on the rise
AGFA
Bayer
Kalle,
Höchst
BASF
CIBA, Sandoz
Decentralization – lack of investment necessitated imitation, competition among small states
Patent situation – laws difficult to enact, foreign technology not protected, competition increased
Geography – raw materials, transportation in Rhein river valley
Education – the Liebig tradition supplied fresh ideas, trained chemists
Unification in 1871 – Patent Act of 1876 arrived at the right time
Business – ties between industry and universities established quickly
-------------------------------------------------------------------------------------------------------Education – Universities and the Technische Hochschule
1809 Univeristy of Berlin – model for a modern university:
Seminars
Semesters
Vernacular
Professional training, productive citizens
Liebig's pedagogical model:
Close relationship with professor, whose enthusiasm evoked admiration and loyalty
Full enthusiasm for studies – 6 days/wk, 12-15 hrs/day
Competitive atmosphere among students
"ample opportunities of witnessing, in a comparatively short time, a vast variety of
processes which are being constantly carried on in an institution consisting of a great
number of experimentalists" (Hofmann, 1849)
1860s – glut of doctoral students led to technische hochschule:*
Proximity to state centers
Ties with state and industry
Included education in other fields
Stimulated improvements at universities (v. similiar by 1900)
Ties with professors highly sought after by companies
5
1870s – Heinrich Caro exemplifies industrial and academic cooperation
As director of research at BASF, Caro tirelessly fostered ties with academics
1868 – Graebe and Liebermann consult Caro regarding alizarin
1873 – Adolf von Baeyer and Caro collaborate on research program
They discover eosin
Martius at Agfa discovers secret formula with the help of Hofmann
Heinrich Caro
1876 – Caro stymied again with chrysoidine by Martius and Hofmann*
1876 – Griess supplied Caro with samples from azo coupling reactions
1878 – Emil and Otto Fischer (under von Baeyer) solve structure of triphenylmethine dyes, but
only with help from Caro
Br
HO
Br
O
O
Br
Br
CO2 H
Eosin
Emil Fischer
Adolf von Baeyer
A. W. Hofmann
-----------------------------------------------------------------------------------------1870-1890 – Rise of the industrial research laboratory and the Bayer example
Research labs enabled acceleration of research by consolidating resources
Teams
Facilities
Academically trained scientists in management positions
Bayer was slower to innovate than other major german firms
By 1882, a full research staff was still not established
1884 –Duisberg enables Bayer to compete with Agfa
Carl Duisberg
Duisberg spontaneously evolves into a research director
Primitive labs replaced with Duisberg design of new building, layout adopted almost universally*
Also quality control, library, conferences, product testing
In 1896, 1 in 70 dyes approved for production
By 1900, 1 in 200 dyes marketed
ca. 1905, 1 in 300 dyes marketed
NH2
N
N
NH2
N
N
SO3 Na
benzopurpurin 4B
Bayer laboratories after Duisberg
SO3 Na
6
Indigo side note
O
N
H
Natural sources were not quickly overcome due to synthetic challenges
1869- von Baeyer proposes correct structure, synthesized 11 years later
H
N
O
von Baeyer:
O
O
HNO3
O
Zn-HCl
OH
NO2
OH
HO
O
N
H
PCl3 , P,
FeCl3
Sn-HCl
indigo
N
H
N
H
N
H
Cl
O
O
O
O
O
NH2
N
HNO2
-H2 O
OH
NH2
isatin
1893 – Heumann's first commercially viable synthesis for BASF
O
H2 SO 4, !
HgSO4
O
NH3
O
N
H
O
NH
O
OH
O
O
NaOCl
O
OH
NH2
NaOH
200 °C
OH
OH
Hofmann
rearrangement
O
Cl
N
H
O
OH
OH
-CO 2
Air
Indigo
N
H
OH
indigofera tinctoria
--------------------------------------------------------------------------------------------------------The industry up to the war – paving the way for IG Farben
Expansion
Germany's coal tar dye exports:
Quantity in tons
Value in thousands of marks
1882
8,363
69,306
1887
14,666
55,534
1892
23,202
70,976
1897
35,510
90,896
1902
59,862
138,582
1907
79,215
186,515
1912
93,671
209,166
Other fields
Chemistry in the service
of industry
Pharmaceuticals – growth of medicine
Heavy chemicals and organic intermediates – industrial efficiency
Photography
Nitrogen fixation – BASF fertilizers and munitions
Isoprene polymerization – Bayer synthetic rubber
7
-----------------------------------------------------------------------------------------War, cartel formation and IG Farben
Intensification of competition led to profits inadequate for investment
1881 – first alizarin cartel fixed price and allocated market
1900 – second alizarin cartel allowed prices of some products to remain low, in exchange for an
international monopoly
Duisberg pushes for fusion of research laboratories, but emphasizes decentralization
1904 – Bayer, BASF, and Agfa, and Höchst and Casella merged as two syndicates
1914 – war turned the industry to explosives, nitrogen and rubber
1916 – exigencies of war brought about merger of the two syndicates to IG Farben
Agreement, stratification, planning enabled further growth of cartel during and after the war
1925 – cartel became a full trust triggering further expansion
Facilitated WW2
IG Farben administrative building - 1928
8
Back to the mosquito
H
NH
H
O
1918 – Paul Rabe takes quinotoxine to quinine
N
HO
MeO
MeO
N
N
quinotoxine
1944 Woodward and Doering's plan
H
NH
Rabe
N
HO
NH
O
MeO
MeO
O
N
N
homeroquinene
quinotoxine
HO
H
HO
N
7-hydroxyisoquinoline
----------------------------------------------------------------------------------------
Woodward's Quinotoxine synthesis
NH
O
HO
CH2O
piperidine
MeOH
N
MeO
MeOH/NaOMe
220 °C, 10h
N
HO
HO
N
N
64%
N
7-hydroxyisoquinoline
1. H2 , PtO
AcOH
2. Ac2O, MeOH
H2 Raney Ni
quant
O
HO
O
N
95% (for 2 steps)
O
H
O
CrO3
HO
N
N
EtOH/NaOEt
EtONO
68%
H
mixture of isomers
HO
N
O
H
N
O
N
N
90%
42%
H
EtO
O
N
NH2
NH
H
HO
O
O
O
H
1. 0.1 N HCl
!
2. AgO, H2 S
quant
H
HO
H
EtO
O
H
1. 60% NaOH
40 °C
2. KOCN
H
MeI, K2 CO 3
EtOH
36% cis recrystallized
homeroquinene
O
O
96%
EtO
N
H
EtO
O
O
MeO
H
1. EtOH, HCl
2.BzCl, K2 CO3
OEt
Ph
N
NaOEt, !
O
N
H
O
6 N HCl, !
H
MeO
N
Ph
quinotoxine
50% (2 steps)
9
Conclusions
NH
H
O
HO
MeO
N
MeO
N
N
quinotoxine
While dye chemistry is a limited field, it facilitated the development of organic
chemistry, chemical industry, chemical education as we know them today.
10