The dark blue color indigo , and the dye of the same name and color , are surely

quite familiar to
the reader . Intense colors in materials indicate a high degree of light absorption by their
component atoms or molecules . That in turn implies an extensive electron resonance and
delocalization in their molecular orbitals . Such a widespread electron resonance and
delocalization is found in metallic solids , a topic of particular interest to me . Thus , new types
of metallic compounds will be more likely derived from highly colored compounds like indigo ,
rather than from colorless ones like the saturated hydrocarbons , for example . Possible
electrically-conductive indigo derivatives are examined further on in this web page .
The terms indigo and indigotin are generally considered to refer to the same chemical substance ,
2,2'-bis(2,3-dihydro-3-oxoindolyliden) [underlined blue hyperlinks can be clicked when online
to download the referenced document , which will open in a new window] . Sometimes the term
indigo is applied only to the color and the natural product (which invariably contains a number
of chemical compounds) , while the word indigotin is reserved for the single pure compound of
indigo . However , Farris apparently uniquely has made an important distinction between the
two terms [the references are presented at the end of the text , below] , as illustrated in the
following sketch :
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As pointed out by Golding and Pierpoint , the indigo molecule (trans , E) is energetically
stabilized by intramolecular hydrogen bonding . Conversely , the indigotin molecule (cis , Z) is
destabilized by repulsion between the lone pairs of electrons on its carbonyl groups , and so far
has never been either isolated from natural sources nor synthesized in a pure form . As will be
discussed later on , it might be possible to obtain the indigotin isomer , but only bonded (via its
nitrogen atoms) to a suitable Transition metal cation such as Cu
2+
to form the compound
copper(II) bis(indigotin) . The distinction made by Farris between indigo and indigotin will be
observed in this web page .
Indigo is chemically related to the heterocyclic compound indole :
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This relationship is also shown in the structure of the natural product indican (mainly from
Indigofera plants) , from which indigo dye was produced in Asia for centuries , before being
displaced by synthetic product from European (mainly German) chemical companies :
Indigo is also biosynthesized in the human body from tryptophan , an amino acid humans share
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with plants . Tryptophan is degraded by intestinal bacteria to the smelly indole . Some of the
indole is converted into indoxyl , which is eliminated via the kidneys . In rare cases certain
people are unable to process the indoxyl properly , and it's oxidized and dimerized into indigo
and indirubin (a red dye) . Traces of the indigo are excreted in their urine . King George III
(1738-1820) of Great Britain apparently was affected by this peculiar syndrome . A related
medical condition , PUB (purple urine bag syndrome) , is thought to occur by the presence of
indigo (blue) and indirubin (red) in the urine . Their combination produces its striking purple
color . PUB is graphically illustrated in the color photo in the medical report on the topic by
Khan and co-workers .
The chromophore is the atomic grouping within a dye molecule responsible for its light
absorption properties . Indigo's chromophore has been shown to be its central part , without the
phenyl groups :
In this web page we'll survey how indigo has been (and still is) chemically produced , and we'll
try to devise new methods to synthesize this remarkable molecule . These new synthetic
strategies may in some cases permit the design of novel analogues of the original molecule ,
having varying degrees of electron resonance and delocalization . Such indigo analogues would
be interesting new dyes to prepare and study , and could provide additional insight into the
electronic structure and functioning of the indigo chromophore .


The prominent German chemist Adolph von Baeyer (1835-1917) was the first person to
determine the molecular structure of indigo (1865-70) and to synthesize it for the first time (in
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1870 , from isatin) . He also prepared it from cinnamic acid , but neither synthesis route was
economically feasible for large scale production :
His third indigo synthesis , from 2-nitrobenzaldehyde (1882) , was simple and gave a good yield
of product , but again was economically impractical due to the high cost of the starting material ,
2-nitrobenzaldehyde . Because of its simplicity and easiness to carry out , this route to indigo ,
now commonly called the Baeyer-Drewson process [von Baeyer's partner's name in this work
was actually spelled Drewsen , but somehow got changed along the way] , is frequently found as
a semi-micro organic chemistry experiment in undergraduate laboratory manuals :
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Adolph von Baeyer was awarded the Nobel Prize for chemistry in 1905 in recognition of his
work on indigo , among his many other chemical accomplishments . However , economically
practical syntheses of indigo were later developed by a Swiss-German chemistry professor , Karl
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Heumann (1850-1894) , and a German industrial chemist , Johannes Pfleger (1867-1957) .
Heumann's first synthesis , in 1890 , used the industrial chemical aniline as a starting material . It
was converted into N-phenylglycine , which was internally condensed into indoxyl in molten
alkali at ~300 C . The indoxyl was quickly oxidized by atmospheric oxygen , dimerizing into
indigo . Unfortunately , the yield of product was too low by this route to make it commercially
attractive .
His second synthesis at the same time used the more expensive fine organic chemical anthranilic
acid as the starting material . In the same sort of reactions utilized by his first route , Heumann
obtained a high yield of indigo in this alternate procedure . It was actually scaled up to an
industrial level (several thousands of tonnes per annum , TPA) by BASF and Hoechst :
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Several years later (in 1901) , Pfleger working for Hoechst modified Heumann's first method
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by adding sodamide (sodium amide , NaNH
2
) to the alkaline flux . Sodamide is a very powerful
dehydrating agent , and it drove the ring closure reaction , to form indoxyl , to completion . Use
of the relatively cheap aniline as the starting material , and of sodamide as the condensation
agent , were the two key factors in the economic success of the BASF-Hoechst industrial indigo
synthesis . In 1925 BASF researchers devised an improved synthesis of N-phenylglycine from
the N-methylolation of aniline with formaldehyde and hydrogen cyanide , followed by
saponification of the resulting nitrile intermediate . This modification provided an additional
economy in the overall indigo production method . The BASF-Hoechst chemical synthesis of
indigo has entirely supplanted its original agricultural source at this time . About 17,000 TPA of
indigo are currently manufactured , virtually all of which is used for dyeing the cotton fibers of
denim , used in blue jeans .


All of the above indigo syntheses , while perfectly functional and you really can't argue with
success , can you ? seemed to me to be unintuitive , that is , with little if any connection to
conventional organic synthesis . And let's be honest : fusion of your intermediate in molten alkali
at 200300 C is definitely not part of the standard organic synthesis repertoire ! Those sorts of
conditions are fully the consequence of industrial expediency . Although indigo (its
chromophore in particular) has a somewhat unusual molecular structure , its synthesis should
nevertheless be amenable to more ordinary organic chemistry procedures than current industrial
processes might suggest . In the following sections of this web page several proposals for a
simpler , more intuitive synthesis of indigo will be outlined . In his review of indigo Farris
mentions ,
There are over thirty different synthetic routes to indigo reported in the chemical literature (p.
367) .
I believe the following proposed methods are novel , but without a thorough literature search in
either Chemical Abstracts or SciFinder Scholar which are no longer available to me I can't
guarantee they actually are .
The two starting materials , as with the commercial processes outlined above , are anthranilic
acid (2-aminobenzoic acid) and aniline . The former is considered to be a fine chemical and is
considerably more expensive than aniline , which is a high tonnage bulk chemical . Nevertheless
, I'll disregard the economic considerations in this study of indigo , in which the chemical aspects
of the compound are emphasized , and open the discussion with synthesis routes to it from
anthranilic acid .
Two points of practical significance must be raised , however . First , the commonest precursor
to indigo is indoxyl (see the sketch near the top of this web page) . Thus , all conventional indigo
syntheses are really indoxyl syntheses , since the latter intermediate is very easily converted into
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indigo by air oxidation . Throughout this essay I present the indoxyl structure in its keto form ;
its enol form is the heterocyclic molecule 3-hydroxyindole (as the aglycon in the indican
molecule , sketched above) .
The second point is also quite relevant to any indigo synthesis . Indigo is a remarkably robust
molecule , chemically speaking . For example , it can be dissolved in concentrated sulfuric acid ,
with the subsequent sulfonation of its aromatic rings (to produce indigo carmine , another useful
dyestuff) . Note that the chromophore is unaffected by this severe treatment . I suspect that the
entire indigo molecule , not only its phenyl rings , are (4n+2) p aromatic (n =1) , and thereby is
stabilized electronically to a certain extent :
The five-membered rings would have an aromatic stabilization somewhat like the pyrrole
molecule , for example . This energetic stabilization can assist us in the synthesis of indigo . In
fact , aromatic stabilization in the indigo product may be the main reason why the oxidation of
indoxyl and its dimerization into indigo is such an extraordinarily facile process . We can utilize
this energetic driving force in the syntheses described in the following sections to promote the
formation of the unusual chromophore section of the indigo molecule .
In the first suggested new synthesis of indigo from anthranilic acid , the CH
2
group in the
indoxyl intermediate would be derived from the N-methylolation of the anthranilic NH
2
group
by formaldehyde (as in the 1925 BASF synthesis of N-phenylglycine) . In the first variation of
this route a phosphorus(III) compound would be attached to the CH
2
group . Phosphorus has
a powerful affinity for oxygen , and the phosphorus(III) center might bond to one of the oxygen
atoms of the anthranilic COOH group and tear it off the carbon . An analogous reaction is the
Wittig olefination reaction , and in particular the Horner-Wadsworth-Emmons modification of
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the Wittig reaction , in which the phosphite group extracts the aldehyde or ketone oxygen atom :
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Triethyl phosphite , (EtO)
3
P (b.p. 156 C) , is a deoxygenating reducing agent , as are all
phosphorus(III) compounds . Triphenylphosphine is an even stronger deoxygenating agent than
the phosphite esters , but its reaction by-product , triphenylphosphine oxide , is only slightly
soluble in water and thus might be difficult to separate from the insoluble indigo product . On
the other hand , triethyl phosphate is water-soluble and so wouldn't interefere with the filtration
of the indigo . The chemically reducing and deoxygenating acids , phosphorus (H
3
PO
3
) and
hypophosphorus (H
3
PO
2
) , are commercially available and might also be successfully used in the
N-methylolation reaction and subsequent deoxygenation reaction . Anthranilic acid is sparingly
soluble in cold water , more so in hot water , so the entire one pot reaction might be carried out
in aqueous solution , possibly with some warming . It could be as simple and easy to do as the
Baeyer-Drewson reaction with 2-nitrobenzaldehyde .
The intermediate methylol-lactone could also be prepared and isolated pure in one step , then
cooked with triethyl phosphite to remove the lactone oxygen , forming indoxyl in the second
step . This intermediate could be isolated pure (under an inert atmosphere such as nitrogen) , or
converted to indigo without any attempted purification .
Noting that in these reactions the methylol-lactone undergoes first a deoxygenating reduction ,
then an oxidizing dehydration , the question arises : could it be dehydrated directly to indigo ?
As mentioned above , formation of the remarkably stable aromatic chromophore system in the
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indigo product might energetically assist the reaction to completion . I may be optimistically
daydreaming here , but just cooking anthranilic acid with formaldehyde under dehydrating
conditions might produce indigo in a good yield ! Now , wouldn't that be a nice improvement
over the BASF-Hoechst process ! The formaldehyde would certainly N-methylolate the
anthranilic acid ....... then what would happen ?
In a second series of experiments the ester , methyl anthranilate , would be the starting material .
Methyl anthranilate is used extensively as a flavoring agent (grape flavor) and perfumery
ingredient (it's a component of bergamot , jasmine , neroli , and ylang-ylang oils , and is found in
grape juice) . Examining Heumann's version 2 industrial synthesis of indigo (sketch above) , we
see that it's a rather severe , forcible type of ring condensation reaction , somewhat like the
well-known Dieckmann reaction (1894-1901 , later than Heumann's indigo synthesis in 1890) .
So the question naturally arises : why not use the genuine Dieckmann reaction to prepare
indoxyl ?
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The same sort of reactions might be applied to the syntheses of thioindigo , a well-known indigo
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analogue , and its oxygen analogue I've dubbed oxyindigo. This latter compound might be
derived from methyl salicylate , which is commonly known as oil of wintergreen , a fragrant
flavoring and scenting chemical . Electron resonance in the oxyindigo chromophore is expected
to be less strong than in either of indigo or thioindigo , as the heteroatom basicity decreases in
the order N >S >O . Thioindigo is actually a red dye (its industrial name is Vat Red 41) , so
oxyindigo could conceivably be colorless !
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In the two sketches above the strong base sodium methoxide (in anhydrous methanol) was
suggested for use in the Dieckmann condensations with the methyl esters . However , the
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extraordinarily powerful , non-nucleophilic base potassium hydride , KH , would probably be
the optimum reagent for these cyclizations . Brown has described the kaliation of esters with
KH , resulting in their condensation into b-ketoesters in very high yields , typically >95% . The
KH reagent was used in the form of a 40% suspension (by weight) in mineral oil , with
anhydrous THF as the reaction solvent .


As outlined above , the modern industrial syntheses of indigo are based on the economical
aniline feedstock , rather than on the more expensive anthranilic acid . Another good reason to
use aniline as a starting material for any new indigo synthesis is that many substituted anilines
are commercially available , and might be used to prepare their corresponding indigo analogues
for study . Such is not the case for anthranilic acid derivatives , which can be challenging to
obtain .
The following proposed synthesis of indigo and its analogues starts with an acetylene chemical ,
dimethyl acetylenedicarboxylate . This material is a moderately priced commercial reagent (eg.
Aldrich Chemical Co.) . Interestingly , BASF produces certain related acetylene chemicals such
as 2-butyne-1,4-diol by the methylolation of acetylene with formaldehyde under alkaline
conditions . It's therefore conceivable that dimethyl acetylenedicarboxylate could also be
manufactured in bulk quantities from acetylene should the demand ever arise for it .
Aniline is used in this acetylene route instead of anthranilic acid . Unlike previous syntheses of
indigo , this proposed procedure does not involve indoxyl as an intermediate . If successful , this
approach could be used to synthesize many other indigo analogues as well :
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NB : Caution ! The intermediate dimethyl E-2,3-dibromofumarate is probably a very hazardous
, lachrymatory , vesicant , corrosive material , and should NOT be isolated . All necessary safety
precautions should be observed (gloves , goggles , efficient fume hood , etc.) when handling its
solutions . I would ask any reader attempting this reaction to please be very careful with it !
In the above synthesis scheme the Friedel-Crafts acylation of the aniline rings is done by the
carbomethoxy ester groups . Acid chlorides , anhydrides , carboxylic acids , and esters can all be
used to acylate aromatic rings ; of course , the acid chlorides are the best known of these
acylating reagents . An interesting example of the acylation/alkylation of an aromatic ring by an
ester function is provided by the synthesis of a-tetralone , by the combination of benzene with
g-butyrolactone . A large (~4:1) molar ratio of AlCl
3
to g-butyrolactone was used in this
preparation , since the Al
3+
acted both as a catalyst in the acylation and as a reagent in the
alkylation , bonding with the alcohol (lactone) oxygen .
In a variation of this proposed reaction , acetylene dicarboxylic acid could be used as the starting
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material , with the COOH groups acylating the aniline rings . Hartough has demonstrated the
acylation of thiophenes and furans with carboxylic acids , using phosphoric acid and phosphorus
pentoxide as the dehydrating agents (presumably the reactive acylium cation is the actual
acylating agent) . Even concentrated sulfuric acid can be an effective dehydrating agent for
acylations by carboxylic acids , for example in the preparation of acridone . As suggested above ,
formation of the energetically stabilizing aromatic indigo chromophore might help to drive these
ring acylations to completion in a good yield .
The highly reactive dimethyl E-2,3-dibromofumarate intermediate could be combined with a
wide variety of aliphatic and aromatic amines (triethylamine is added to the aniline or other
amine to absorb the by-product HBr) . For example , an aliphatic version of the indigo
chromophore could be produced using dimethylamine as the amine reactant :
The resulting adduct , dimethyl 2,3-bis-E-(dimethylamino)fumarate , might have a deep blue
color . However , it might equally be colorless , since the chromophore in this case isn't part of
an aromatic ring system , as with indigo .
The hypothetical compound pseudo-indigo (for lack of a better term) has the indigo
chromophore and it should also be aromatic . Its rings have six p electrons each , even though it
lacks the phenyl groups . The following scheme is suggested for the synthesis of pseudo-indigo .
Its key step is the Mannich condensation of 3-hexyne-2,5-dione with two equivalents of
formaldehyde and ammonium cation (in effect , the transient methylol intermediate
HOCH
2
NH
3
+
) , followed by the a,b-addition of the neutral amino groups to the reactive triple
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bond :
As an alternative to bromination / dehydrobromination to achieve aromaticity in the pseudo-
indigo , dehydrogenation of the bis-aminoketone intermediate might be accomplished with
palladium on charcoal , or with sulfur or selenium . All three reagents are well known
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dehydrogenation agents used in organic syntheses .
I suspect that 4n+2 p aromaticity is required for the indigo chromophore , even though the
phenyl groups are unnecessary . Thus , pseudo-indigo will likely have a dark blue color like
indigo itself , while dimethyl 2,3-bis-E-(dimethylamino)fumarate will be colorless .
The readily available fine chemical 3-bromoaniline (b.p. 251 C) might serve as the precursor to
the legendary Tyrian Purple dye , 6,6'-dibromoindigo :
If successful , this acetylene route to Tyrian Purple would be very simple and straightforward ,
much more so than the many lengthy and convoluted syntheses of the compound reported in the
literature (see the refs. in Tyrian Purple) . And , given the dozens of substituted anilines
commercially available , the acetylene route would make many other interesting indigo
analogues readily available for study .
Wurtster Blue compounds also have a deep , sapphire blue color , caused by the molecule-wide
resonance of their unpaired singlet electron , formally located on their aminium nitrogen atom :
It might be possible to synthesize an indigo Wurster Blue compound from the intermediate
5,5'-bis(dimethylamino)indigo by treating it with a suitable one-electron oxidizer such as
antimony pentachloride :
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A powerful one-electron oxidizer , the nitrosonium cation NO
+
(as its stable salt NO
+
PF
6
-
) ,
could be used to form the corresponding Wurster Blue compound ,
5,5'-bis(dimethylaminium)indigo hexafluorophosphate . The extreme degree of electron
resonance in these hypothetical Wurster Blue molecules might cause them to appear black !
They might also be electrically conducting to a certain extent , conceivably having the electron
transport properties of a moderately conductive semiconductor . If so , their synthesis and study
would be a promising venture into the fascinating realm of the metallic solids .
The unusual indigo chromophore with its combination of two electron-donating nitrogen atoms
and two electron-withdrawing carbonyl groups suggests that indigo could form charge transfer
compounds with either electron acceptor or electron donor molecules . Examples of both types
of compounds are illustrated as follows :
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In an undergraduate analytical chemistry course I had to prepare crystalline derivatives of an
unknown organic compound , so I made its charge transfer complexes with trinitrobenzene and
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picric acid , which together with its various spectroscopic analyses (IR , UV/VIS , NMR)
confirmed its identity as naphthalene . Of course , it also smelled like mothballs , which was an
immediate olfactory clue !
Tetrakis(dimethylamino)ethylene [TDAE] and tetrathiofulvalene [TTF] belong to the class of
electron-rich olefins , and are remarkably powerful one- and two-electron reducers . In fact ,
TDAE is said (Hoffmann , electron-rich olefins , p. 756) to be a reducing agent comparable to
zinc metal (E
ox
0
=0.76 V) . It can form electrically-conducting charge transfer compounds with
various acceptors :
TTF forms a mixed-valent charge transfer compound with TCNQ (above sketch) in which there
are both TTF
0
molecules (41%) and TTF
1+
cations (59%) . TTF-TCNQ is a molecular metal ,
with an ambient electrical conductivity of ~9000 ohm
-1
-cm
-1
at 58 K ; below that temperature
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the conductivity plummits , and the material becomes an insulator . Above 58 K TTF-TCNQ
behaves like a conventional metal :
As mentioned , the indigo chromophore appears to be electrically amphoteric , with electron-
donating N atoms (S atoms in thioindigo) and electron-accepting C=O groups . It's interesting to
speculate that indigo might form electrically-conductive charge transfer compounds with TDAE ,
TTF , TCNQ , TCNE , and other such electron donor and acceptor molecules . If they had a
significantly high electrical conductivity they might even be classified as molecular metals !
One of the challenges presented by the synthesis of such charge transfer compounds is the
notorious insolubility , or low solubility , of indigo in water and most common organic solvents .
It will dissolve to a certain extent in chloroform , dimethyl sulfoxide , and nitrobenzene . The
metallic TTF-TCNQ charge transfer complex was prepared by mixing solutions of the TTF and
TCNQ components in acetonitrile . I wonder if the common paint solvent acetone would
dissolve indigo to any extent . The very polar solvent propylene carbonate , which has been used
to dissolve various inorganic salts in electrochemical studies , might also be tried as an indigo
solvent .

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The nucleophilic N [NH] and O [C=O] sites on the indigo molecule might be used to form
coordinate covalent bonds with suitable electrophilic acceptors such as metal cations ,
particularly those from the Transition metal families . The first Transition metal complexes with
indigo as a ligand were prepared by Beck and co-workers around 1989 . More recently ,
Professor R.G. Hicks and his students at the University of Victoria , British Columbia , Canada ,
have developed a new series of indigo-based ligands for complexation with Transition metal
cations . These so-called nindigos, which are bi-funcionalized ketimines , were prepared by
the rather forceful condensation of indigo with anilines : 2 RNH
2
+2 (indigo)C=O -------->2
RN=C(indigo) +2 H
2
O . The nindigo reagents are more soluble in organic solvents than indigo
, they are more reactive and versatile as ligands than it , and their metal cation complexes are
easier to analyse and characterize than are those of indigo .
In Beck and co-workers' indigo-Pd/Pt complexes the indigo served as a monodentate ligand ,
with the Pd/Pt bonded by the carbonyl oxygen and the amine nitrogen . Tributylphosphine and
chloride ligands on the Pd/Pt improved the solubility of the complex in organic solvents [the
bis(indigo) complex was very insoluble] . A similar sort of metal-indigo complex might be
formed with Cu(II) :
The copper(II) cation in this hypothetical complex would have a tetrahedral (sp
3
) coordination .
These Transition metal coordinate covalent compounds of indigo are reminiscent of the
phthalocyanine-metal complexes , which are highly insoluble in water and organic solvents , and
are accordingly used as dyes and pigments in many applications . Copper(II) phthalocyanine is a
dark blue solid ; its trade name is Monastral Blue (ICI) :
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The corresponding bis-indigo complex with copper(II) might be prepared via the leuco forms of
indigo and indigotin . The complexation would take advantage of the powerful bonding affinity
between the copper(II) cation and four amine nitrogen atoms (overcoming the destabilizing
carbonyl oxygen lone pairs repulsion) :
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The resulting compound , copper(II) bis(indigotin) , could well be a deep blue , highly insoluble
, microcrystalline solid like copper(II) phthalocyanine , and might find the same industrial uses
as it . On a practical note , copper(II) bis(leucoindigotin) and copper(II) bis(indigotin) might be
tried as the insoluble blue pigment for dying cotton and other textiles . In effect , the copper(II)
salt would be used in the conventional indigo dying process as a mordant , to permanently bond
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the dye molecules onto the fiber surfaces . Such copper(II) indigo complexes might deposit a
deeper , more intense shade of blue on the textile than ordinary indigo , and be more resistant to
oxidation and fading than it .
The corresponding nickel(II) bis(indigotin) , with square planar , low spin , diamagnetic Ni
2+
(3d
8
) , could be prepared in a similar manner . I'm guessing it would have a deep green color .
These examples will give the reader a glimpse into the new research area of indigometal cation
complexes .
I hope this web page has shown that there's a lot more to indigo chemistry than just blue jeans !


A comprehensive bibliography of the literature of indigo has been compiled by : C.J. Cooksey ,
Indigo : An Annotated Bibliography, Biotechnic and Histochemistry 82 (2) , pp. 105-125
(2007) . It contains a wealth of information about indigo from natural sources , and of the many
syntheses and physical and chemical properties of the compound . Update (August 14
th
, 2012) :
a revised version of this bibliography has just been published : C.J. Cooksey , An Annotated
Bibliography of Recent Significant Publications on Indigo and Related Compounds, Biotechnic
and Histochemistry 2012 , Early Online , pp. 1-25 . Complimentary PDF copies of these
bibliographies can be obtained via email by writing to Dr. Cooksey .
Farris : R.E. Farris , Dyes , Natural, pp. 351-373 in the Kirk-Othmer Encyclopedia of
Chemical Technology , 3
rd
edition , vol. 8 , M. Grayson and D. Eckroth (eds.) , John Wiley ,
New York , 1979 . Indigo is discussed on pp. 364-368 . Indigotin is structure 46 , p. 367 .
Golding and Pierpoint : B.T. Golding and C. Pierpoint , Indigo Blue, Educ. Chem. 23 (3) , pp.
71-73 (May , 1986) .
indole : Y. Yamamoto , Y. Inoue , U. Takaki , and H. Suzuki , Development of a Practical
One-Pot Synthesis of Indigo from Indole, Bull. Chem Soc. Jpn. 84 (1) , pp. 82-89 (2011)
[HTML , 100 KB] .
apparently was affected : C. Cooksey and A.T. Dronsfield , George III , Indigo , and the Blue
Ring Test, Educ. Chem. 45 (2) , pp. 45-47 (March , 2008) [web page] .
Khan and co-workers : F. Khan , M.A. Chaudhry , N. Qureshi , and B. Cowley , Purple Urine
Bag Syndrome : An Alarming Hue ? A Brief Review of the Literature, Int. J. Nephrol. 2011 ,
Article ID 419213 , 3 pp. [PDF , 958 KB] .
Indigo's chromophore : C.J. Cooksey , Tyrian Purple : 6,6'-Dibromoindigo and Related
Compounds, Molecules 6 (9) , pp. 736-769 (2001) ; Figure 2 , p. 745 [PDF , 302 KB] .
Several New Aspects of Indigo Chemistry http://www.chemexplore.net/indigo.htm
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synthesize it : anon. (Web document) , The History of Indigo, Department of Chemistry ,
University of New Brunswick , Fredericton , New Brunswick , Canada [PDF , 314 KB] .
laboratory manuals : The History of Indigo (above) , PDF p. 5 ; anon. (Web document) ,
Chemistry of Blue Jeans : Indigo Synthesis and Dyeing, p. 8 [PDF , 106 KB] ; B. English et al.
, Synthesis of Indigo and Vat Dyeing , Exp. 863, p. 3 [PDF , 145 KB] ; anon. (Web document
from the Royal Society of Chemistry , UK) , The Microscale Synthesis of Indigo Dye, PDF p.
3 [PDF , 24 KB] ; C.J. Cooksey , Indigo Chemical Synthesis [web page] .
sodamide : the sodamide fusion process is described in some detail by W.C. Fernelius and E.E.
Renfrew , Indigo, J. Chem. Educ. 60 (8) , pp. 633-634 (1983) ; see esp. p. 634 .
anthranilic acid : P. Wiklund and and J. Bergman , The Chemistry of Anthranilic Acid, Current
Org. Syn. 3 (3) , pp. 379-402 (2006) ; B.S. Furniss et al. , Anthranilic Acid, Vogels Textbook
of Practical Organic Chemistry , 4
th
edition , Longman , London (UK) , 1978 ; p. 666 ; G.
Kilpper and J. Grimmer , Continuous Production of Anthranilic Acid, U.S. Patent 4,276,433
(to BASF , June 30
th
, 1981) [PDF , 185 KB . Note : this file can be opened only with Acrobat
Reader v. 6 or later . If desired , this application can be downloaded for free from
Oldversion.com] . The following sketch , abstracted from this patent , outlines the industrial
manufacture of anthranilic acid from phthalimide using the Hofmann reaction (or rearrangement
or degradation) :
Cooksey (web page) provides a broader perspective on this anthranilic acid route to indigo ,
Several New Aspects of Indigo Chemistry http://www.chemexplore.net/indigo.htm
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starting with the bulk industral chemical naphthalene .
Horner-Wadsworth-Emmons modification : W.S. Wadsworth Jr. and W.D. Emmons , The Utility
of Phosphonate Carbanions in Organic Synthesis, J. Amer. Chem. Soc. 83 (7) , pp. 1733-1738
(1961) ; web page (1) ; web page (2) .
Dieckmann reaction : J.P. Schaefer and and J.J. Bloomfield , The Dieckmann Condensation
(Including the Thorpe-Ziegler Condensation), Org. React. 15 , pp. 1-203 (1967) ; N. J. Leonard
and C. W. Schimelpfenig Jr. , Synthesis of Medium- and Large-Ring Ketones via the Dieckmann
Condensation, J. Org Chem. 23 (11) , pp. 1708-1710 (1958) ; E.E. Royals , Claisen
Condensation of Methyl Esters, J. Amer. Chem. Soc. 70 (2) , pp. 489-491 (1948) [similar
reaction conditions are used in both the Claisen and Dieckmann condensations] ; M.A.A. Amleh
, Dieckmann Condensation Reaction, Microsoft Powerpoint Slide Show [PPT , 259 KB] ; P.S.
Pinkney , 2-Carboethoxycyclopentanone, Org. Syn. Coll. Vol. 2 , pp. 116-119 (1943) [PDF ,
140 KB] ; H.U. Daeniker and C.A. Grob , 3-Quinuclidone Hydrochloride, Org. Syn. Coll. Vol.
5 , pp. 989-993 (1973) [PDF , 142 KB] ; J. T. Mohr, M. R. Krout, and B. M. Stoltz ,
Preparation of (S)-2-Allyl-2-Methylcyclohexanone, Org. Syn. 86 , pp. 194 et seq. (2009)
[web page] ; Organic Chemistry Portal [web page] ; SynArchive [web page] ; Classic Organic
Reactions [web page] .
Brown : C.A. Brown , Rapid , High Yield Condensations of Esters and Nitriles via Kaliation,
Synthesis , May , 1975 , pp. 326-327 . The extremely reactive KH can be safely and
conveniently handled as a 50% dispersion (by weight) in paraffin wax : D.F. Taber and C.G.
Nelson , Potassium Hydride in Paraffin : A Useful Base for Organic Synthesis, J. Org Chem. 71
(23) , pp. 8973-8974 (2006) [PDF , 35 KB] .
a-tetralone : C.E. Olson and A.R. Bader , a-Tetralone, Org. Syn. Coll. Vol. 4 , pp. 898-902
(1963) [PDF , 171 KB] .
Hartough : H.D. Hartough and A.I. Kosak , Acylation Studies in the Thiophene and Furan
Series . IV. Strong Inorganic Oxyacids as Catalysts, J. Amer. Chem. Soc. 69 (12) , pp.
3093-3096 (1947) ; idem. , Acylation Studies in the Thiophene and Furan Series . VI. Direct
Acylation with Carboxylic Acids and Phosphorus Pentoxide, J. Amer. Chem. Soc. 69 (12) , pp.
3098-3099 (1947) ; A.I. Kosak and H.D. Hartough , 2-Acetothienone, Org. Syn. Coll. Vol. 3 ,
pp. 14-16 (1955) [PDF , 115 KB] .
acridone : C.F.H. Allen and G.H.W. McKee , Acridone, Org. Syn. Coll. Vol. 2 , pp. 15-17
(1943) [PDF , 129 KB] .
Tyrian Purple : the best review I've read of Tyrian Purple is undoubtedly that by Cooksey
(Indigo's chromophore , above) ; it's highly recommended . The synthesis of Tyrian Purple has
attracted a great deal of attention over the years . Various publications on this topic : P.F. Schatz
, Indigo and Tyrian Purple In Nature and in the Lab, J. Chem. Educ. 78 (11) , pp.
1442-1443 (2001) ; J.M. Pinkney and J.A. Chalmers , Synthesizing Tyrian Purple, Educ.
Chem. 16 (5) , pp. 144-145 (September , 1979) ; J.L. Wolk and A.A. Frimer , Preparation of
Tyrian Purple (6,6'-Dibromoindigo) : Past and Present, Molecules 15 (8) , pp. 5473-5508
Several New Aspects of Indigo Chemistry http://www.chemexplore.net/indigo.htm
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(2010) [PDF , 303 KB] ; idem. , A Simple , Safe and Efficient Synthesis of Tyrian Purple
(6,6-Dibromoindigo), Molecules 15 (8) , pp. 5561-5580 (2010) [PDF , 229 KB] ; Cooksey's
Tyrian Purple web page ; Cooksey's synthesis (web page) ; historical syntheses (web page) ;
Wikipedia web page ; Molecule of the Month web page .
Wurtster Blue compounds : See the discussion , photos , and video demonstration of the
formation of a Wurster Blue compound in solution on Peter Keusch's web page , Wurster's
Blue.
antimony pentachloride : SbCl
5
has been used to form the stable Wurster Blue aminium salt ,
tris-(4-bromophenyl)aminium hexachloroantimonate , in a quantitative yield : F.A. Bell , A.
Ledwith , and D.C. Sherrington , Cation-radicals : Tris-(p-bromophenyl)amminium Perchlorate
and Hexachloroantimonate , J. Chem. Soc. C 1969 (19) , pp. 2719-2720 ; see also G.W.
Cowell , A. Ledwith , A.C. White , and H.J. Woods , Electron-Transfer Oxidation of Organic
Compounds with Hexachloroantimonate [SbCl
6
] Ion , J. Chem. Soc. B 1970 (2) , pp. 227-231
. The standard reduction potential of SbCl
5
in a halide environment is ~0.8 V , indicating that it
is a moderately strong oxidizing agent .
nitrosonium cation : W.J. Plieth , Nitrogen, Ch. 5 , pp. 321-479 in Encyclopedia of
Electrochemistry of the Elements , Vol. 8 , A.J. Bard (ed.) , Marcel Dekker , New York , 1978 ;
p. 325 . The redox half-reaction (reduction) of the nitrosonium cation is :
NO
+
+e
-
--------------> NO (g) ; E
0
red
= 1.45 V .
This standard reduction potential indicates that NO
+
is a rather powerful oxidizing agent .
electron-rich olefins : R.W. Hoffmann , Reactions of Electron-Rich Olefins, Angew. Chem.
Internat. Ed. Engl. 7 (10) , pp. 754-765 (1968) ; N. Wiberg , Tetraaminoethylenes as Strong
Electron Donors, Angew. Chem. Internat. Ed. Engl. 7 (10) , pp. 766-779 (1968) ; J. Hocker
and R. Merten , Reactions of Electron-Rich Olefins with Proton-Active Compounds, Angew.
Chem. Internat. Ed. Engl. 11 (11) , pp. 964-973 (1972) .
TDAE : R.L. Pruett et al. , Reactions of Polyfluoro Olefins. II. Reactions with Primary and
Secondary Amines, J. Amer. Chem. Soc. 72 (8) , pp. 3647-3650 (1950) ; the preparation of
TDAE is described on p. 3649 . TDAE is commercially available , eg. from Aldrich .
TTF-TCNQ : J. Ferraris , D.O. Cowan , V. Walatka Jr. , and J.H. Perlstein , Electron Transfer in
a New Highly Conducting DonorAcceptor Complex, J. Amer. Chem. Soc. 95 (3) , pp.
948-949 (1973) ; D. Dolphin , W. Pegg , and P. Wirz , The Preparation of Protio and Deuterio
Derivatives of the Tetracyanoquinodimethane Tetrathiofulvalene Complex, Can. J. Chem. 52
(24) , pp. 4078-4082 (1974) [PDF , 215 KB . Note : this file can be opened only with Acrobat
Reader v. 6 or later] ; E. Engler , Organic Metals, Chemtech 6 (4) , pp. 274-279 (April , 1976)
; see Figure 1 , p. 275 ; A.J. Epstein and J.S. Miller , Linear Chain Conductors, Scientific
American 241 (4) , pp. 52-61 (October , 1979) ; see esp. pp. 57 and 59 ; M.R. Bryce ,
Tetrathiafulvalenes (TTF) and Their Selenium and Tellurium Analogs (TSF and TTeF) :
Electron Donors for Organic Metals, Aldrichimica Acta 18 (3) , pp. 73-77 (1985) [PDF , 4186
Several New Aspects of Indigo Chemistry http://www.chemexplore.net/indigo.htm
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KB . Note : the entire Issue 3 must be downloaded to obtain the article] .
propylene carbonate : W.J. Peppel , Preparation and Properties of the Alkylene Carbonates,
Ind. Eng. Chem. 50 (5) , pp. 767-770 (1958) . Several physical properties of PC tabulated in this
review : m.p. 49.2 C ; b.p. 241.7 C (note : PC begins to decompose at ~150 C) ; s.g. 1.2057
; dielectric constant , 69.0 ; R. Jasinski , Electrochemistry and Application of Propylene
Carbonate, Adv. Electrochemistry Electrochem. Eng. 8 , pp. 253-335 , P. Delahay and C.W.
Tobias (eds.) , Wiley Interscience , New York , 1971 .
Beck and co-workers : W. Beck et al. , Indigo-Metal Complexes : Synthesis and Structure of
PdII and PtII Compounds Containing the Anions of Indigo and Octahydroindigo as Mono- and
Bis-Chelate Ligands, Angew. Chem. Internat. Ed. Engl. 28 (11) , pp. 1529-1531 (1989) .
nindigos : S.R. Oakley et al. , Nindigo : Synthesis , Coordination Chemistry , and Properties
of Indigo Diimines as a New Class of Functional Bridging Ligands, Chem. Commun. 2010 (46)
, pp. 6753-6755 ; G. Nawn et al. , Redox-Active Bridging Ligands Based on Indigo Diimine
(Nindigo) Derivatives, Inorg. Chem. 50 (20) , pp. 9826-9837 (2011) ; S. Oakley , Synthesis ,
Characterization and Coordination Chemistry of Indigo Diimines, M.Sc. Thesis , University of
Victoria , British Columbia , Canada (2008) [PDF , 1828 KB] ; Research Project Dr. Skye
Fortier [web page] .

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