The synthesis of mauveine A and mauveine B from N-tert-butyl-p-toluidine

Article abstract of DOI:10.3184/174751914X13912601347455

The oxidation of a mixture of N-tert-butyl-p-toluidine/aniline/o-toluidine (1 : 1.5 : 1.5) with K₂Cr₂O₇ in H ⁺/H₂O followed by de-tertbutylation with acid gives mauveine A and mauveine B. These compounds dye silk the same shade of red mauve as that of silk dyed by authentic mauveine.

Full text of DOI:10.3184/174751914X13912601347455

JOURNAL OF CHEMICAL RESEARCH 2014
VOL. 38 MARCH, 163–168
RESEARCH PAPER 163
The synthesis of mauveine A and mauveine B from N-tert-butyl-p-toluidine
M. John Plater*
Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK
The oxidation of a mixture of N-tert-butyl-p-toluidine/aniline/o-toluidine (1:1.5:1.5) with K2Cr2O7 in H+/H2O followed by de-tert-
butylation with acid gives mauveine A and mauveine B. These compounds dye silk the same shade of red mauve as that of silk
dyed by authentic mauveine.
Keywords: mauveine, mauve, tert-butyl, o-toluidine, p-toluidine, dyeing
In 1856, Perkin obtained a purple ethanolic solution of mauveine
by extracting a black precipitate, which had precipitated from
the oxidation of aniline sulfate by potassium dichromate
in water.1 The synthesis of mauveine was commercialised
since it gave silk an attractive purple colour. A factory for
its manufacture and for other dyestuffs was built in 1857 at
Greenford Green which was the beginning of the coal-tar dye
industry.2 Perkin began research on the molecular structure
of mauveine3–6 and later others showed that the core is a
phenazine moiety.7–10 Over a century later, two key components
of mauveine were characterised as mauveine A and mauveine
B by NMR spectroscopy and mass spectrometry.11,12 Further
analysis has also shown the mixture to be more complex with
12 homologues present.13,14 Despite the commercialisation of
mauveine, its synthesis is still seen as a challenge particularly
to get silk the same colour as that dyed using Perkin’s authentic
mauveine.15 Attempts to do this back in 1956 by W.H. Cliffe
and others for the centenary celebrations failed. Silk dyed with
mauveine made and purified by Perkin’s method (the oxidation
of aniline/o-toluidine/p-toluidine mixtures with K2Cr2O7/H+/
H2O) was a blue shade of mauve rather than the red shade
of mauve which was obtained with authentic mauveine. I
have, therefore, examined some different methods of making
mauveine using either N-phenyl-p-phenylenediamine16,17 or
N-alkyl-p-toluidines18 and compared the colours of silk dyed
with these and that dyed with authentic mauveine. Perkin filed
one later patent in 1863 on the alkylation of the leuco-base of
mauveine and commented on its red shade of mauve on silk but
the method does not appear to have been exploited.19
Results and discussion
Synthesis
Scheme 1 shows how mauveine and some derivatives were
prepared by the oxidation of N-alkyl-p-toluidines using
K2Cr2O7. Table 1 summarises the chromophores that have
been prepared. The yields for these reactions are improved
compared to those obtained for the oxidation of aniline/
o-toluidine/p-toluidine mixtures.16 Key intermediate dimers in
the mechanism are shown in Scheme 2. The N-alkyl substituent
probably serves to stabilise an aminyl radical, which reacts with
aniline or o-toluidine by homolytic aromatic substitution.16 The
radical would be stabilised by hyperconjugation from the alkyl
group. The dimers formed are key electron-rich building blocks
which can undergo further oxidation and coupling leading to
tetramers (mauveine).16 Initially I considered that the N-methyl
group at position 3 in compounds 5–7 might be oxidatively
removed by abstraction of hydrogen forming a carbocation
stabilised by a nitrogen lone pair of electrons. This would
R4
R3
N
N
R2
R2
aniline
or
aniline and
K
2Cr2O7
+
H+
/H2O
H2N
N
HN
R1
R1 Me 1
o
-toluidine
R1
=
5-10
R1
Et 2
=
=
R1 iPr 3
=
R1 tBu 4
H+
tBu
/H2O/-
R4
R3
N
R2
H2N
N
N
H
11-15
Scheme 1 The synthesis of mauveine (C25b 11, A 14, B 15) and mauveine derivatives by N-alkyl-p-toluidines.
See Table 1 for the R group substituents. Compounds 12 and 13 were isolated but not separated (see Scheme 5).
* Correspondent. E-mail: m.j.plater@abdn.ac.uk
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164 JOURNAL OF CHEMICAL RESEARCH 2014
H2N
N
aniline
or
aniline and
R1
K
2Cr2O7
+
H+
+
N
HN
R1
R1 Me 1
/H2O
o
-toluidine
R1
=
H2N
R1 Et
=
2
R1 iPr 3
=
N
R1 tBu 4
=
R1
t
R1 = Me, Et, iPr, Bu
Scheme 2 Proposed formation of N-alkyl-N-tolyl-p-phenylene dimers as key intermediates in mauveine synthesis
(see also ref. 17).
Table 1 Summary of the compounds prepared by the oxidation of N-alkyl-
p-toluidines 1–4 with either aniline or aniline and o-toluidine using K2Cr2O7
was unexpected. Interestingly compound 9 with this N-alkyl
substituent gave a better yield of product (Table 1).
R1
R2
R3
R4
Yield/%
Having prepared N-methyl,18 N-ethyl and N-isopropyl
derivatives my attention turned to making an N-tert-butyl
derivative of mauveine. The simplest synthesis of N-tert-
butyl-p-toluidine 4 involves heating the hydrochloride salt of
Compound
5a
Me
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
Me
H
H
H
H
H
Me
6.3
6.0
7.0
3.5
6.0
1
1.1
1.3
3.5
6a
Me
Me
H
H
H
H
Me
Me
7a
8
9
10
11
14b
15b
t
20,21
p-toluidine in BuOH at about 150 °C.
A bulky alcohol
iPr
tBu
H
is advantageous because it only alkylates the amine once. It
also allows a reactive carbocation intermediate to form easily
which can alkylate the amine. Aromatic amines were also
methylated and ethylated this way and are discussed by Perkin
in the Hofmann Memorial Lecture.2 The literature preparation
was repeated to make N-tert-butyl-p-toluidine 4 by heating the
hydrochloride salt of p-toluidine in tBuOH at about 150 °C for
24 h. Analysis by TLC (Et2O:light petroleum, 25:75) showed
an acceptably clean reaction with a new less polar product and
a small amount of p-toluidine left. Heating for shorter periods
can leave more starting material. This crude reaction product
was used directly in the next stage without further purification.
The product in tBuOH was diluted in H2O/H+ and oxidised with
H
H
The yield for compounds 11, 14–15 includes the formation of N-tert-butyl-
p-toluidine and a de-tert-butylation step. Compounds 12 and 13 were
isolated as a mixture in 8% yield (see Scheme 5).
aThe syntheses of compounds 5–7 have been reported previously and are
included for clarity.18
bStarting from purified N-tert-butyl-p-toluidine the combined yield of
mauveine A 14 and mauveine B 15 was 5%.
react with water deprotecting the chromophore. This lone pair
is, however, involved in conjugation to the chromophore and
may not be readily available. Indeed, I was unable to carry out
the oxidation of either the N-methyl group of compound 518 or
the N-isopropyl group of compound 9 in dilute sulfuric acid.
These conditions are more vigorous than those of the parent
synthesis because the acid is stronger without aromatic amines
present. The N-isopropyl group of compound 9 has two extra
methyl groups that would stabilise a carbocation so its stability
t
K2Cr2O7 (Scheme 3). Since BuOH is a tertiary alcohol, it will
not be oxidised by K2Cr2O7. The reaction turned purple after
4–5 h. This is an interesting building block to use in mauveine
synthesis because its steric bulk might stabilise an aminyl free
radical, it cannot easily be oxidised like an isopropyl group,
and, owing to the stability of the tert-butyl carbocation, it might
be deprotected more readily. Steric compression in the product
might also facilitate deprotection.
N
N
CH3
H2N
N
10
CH3
K
2Cr2O7
+
+
aniline
H+
/H2O
N
N
N
CH3
H
4
H2N
N
H
crude material
11
Scheme 3 The oxidation of N-tert-butyl-p-toluidine and aniline with K2Cr2O7.
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JOURNAL OF CHEMICAL RESEARCH 2014 165
N
N
CH3
N
N
CH3
H
N
H+
H2N
10
Compound
H2N
N
H
+
Mauveine C25b 11
Scheme 4 Proposed mechanism for the de-tert-butylation of chromophore 10 catalysed by acid.
1
Standard work-up and chromatography gave initially a
small amount of mauveine chromophore C25b 11 followed by
the major product 10, which had retained the tert-butyl group.
The separation works well as N-alkylated chromophores are
more polar.18 Compound 10 was fully characterised and showed
present at 2.29 ppm (3H) in the H NMR spectrum and only
one alkyl carbon was present at 19.5 ppm in the 13C NMR
spectrum. Product 11 might arise in the reaction from the
oxidative coupling of residual p-toluidine with aniline, or from
in situ loss of the tert-butyl group. Scheme 4 shows a possible
mechanism for the acid-catalysed loss of the tert-butyl group.
Initial protonation of the tertiary nitrogen atom is followed
by loss of a tert-butyl cation. This will be facilitated by
formation of the stable mauveine chromophore. Compound 11
stains silk a so-called blue shade of mauve and is different from
the red shade of mauve on silk stained from 1862 authentic
mauveine. It does, however, resemble the blue shade of mauve
1
typical H NMR and 13C NMR data. A tert-butyl group of 9H
occurred at 1.36 ppm and a single methyl group at 2.4 ppm.
Singlets of 1H for positions 4 and 5 were present at 5.95 and
6.02 ppm. The tolyl ring shows two doublets at 6.94 and
7.26 ppm. The doublet for position 2 is partially masked by the
doublet at 7.26 ppm. The two ortho-phenyl protons occur as a
doublet at 7.47 ppm. Downfield resonances for positions 1 and 8
occurred at 7.80 ppm (masked by the 3-phenyl proton multiplet)
and 7.90 ppm. Despite the bulk of the nitrogen atom at position
3, the spectrum remains well resolved and the compound
is stable. The 13C NMR spectrum showed resonances at 19.8
(Me), 28.8 (CMe3) and 58.8 ppm (N–CMe3). The UV-VIS
spectrum showed λmax at 550 nm and 280 nm showing that the
bulk of the tert-butyl group had not prevented conjugation of
the nitrogen atom to the chromophore. The compound showed
photographed previously, which came from a mauveine rich in
13
mauveine C25b
.
A sample of compound 9 was treated under
identical acidic conditions but was not deprotected and gave
only recovered starting material. The N-isopropyl group is
stable under these conditions.
The reactions shown in Schemes 3 and 4 were then
repeated by oxidising a mixture of N-tert-butyl-p-toluidine/
aniline/o-toluidine with K2Cr2O7 followed by deprotection with
acid. This reaction turned purple after 1 h so was faster and more
efficient. Although two fractions were collected from step 1
(tert-butylated material in 8% yield and a small amount of non-
tert-butylated material) only the final products mauveine A 14
and mauveine B 15 were separated and characterised after acid
treatment of the tert-butylated material (Step 2) (Scheme 5).
t
a strong molecular ion at m/z 433 and a fragmentation of Bu
at m/z 377 (50%). The product 10 was then treated with cHCl
(5 mL) in MeOH (10 mL). The mixture was heated to 40–50 °C
and evaporated to dryness. The tert-butyl group was removed
under these conditions to give product 11 which was fully
characterised spectroscopically. Only one alkyl group was
R4
CH3
STEP 1
2Cr2O7/H+/H2O
R3
N
N
R2
+
aniline and
(i) K
o
-toluidine
N
H
(1.5:1.5)
H2N
N
4
4
12 R2
13 R2
R
R
=
3 = Me,
=
R H
3
4
=
=
=
R
Me
Main products
2
STEP
t
-
Bu
(ii) H+/H2O
R4
R3
N
N
R2
H2N
N
H
4
Mauveine A 14 R2
Mauveine B 15 R2
R
R
Me, R
H
3
=
=
=
=
3
4
=
=
Me
R
Scheme 5 A two-step synthesis of mauveine A 14 and mauveine B 15.
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166 JOURNAL OF CHEMICAL RESEARCH 2014
The intermediate tert-butyl-substituted chromophores 12
and 13 were not separated from each other or characterised.
Mauveine A 14 and mauveine B 15 showed spectroscopic
1
data including H NMR spectra identical to those previously
reported from authentic mauveine.11,14 The combined yields
are slightly higher than that for the formation of mauveine C25b
11. This is typical of reactions that use a mixture of aniline/o-
toluidine rather just aniline. The yields are lower than expected
but two extra steps are included. These are the formation of
the N-tert-butyl-p-toluidine 4 (isolated yield of 62%)21 and
later the de-tert-butylation step to give the product. However,
a similar combined yield of 5% was obtained for a mixture
of mauveine A 14 and B 15 starting from 4 as a pure isolated
starting material. This is preferred because only a trace of the
de-tert-butylated products 14 and 15 is formed in the first step.
These were combined with the main product. This shows that
they must predominantly form from unreacted p-toluidine in
the unpurified starting material 4.
An attempt to synthesise N-tert-amyl-p-toluidine 16, from
tert-amyl-alcohol and p-toluidine hydrochloride, by the same
method used for the formation of N-tert-butyl-p-toluidine 4, was
unsuccessful and gave only recovered p-toluidine (Scheme 6).
The different reactivity of the two tertiary alcohols, or the
stability of the products, is striking.
Fig. 1 Left: Top spot (mauveine B) and lower spot (mauveine A) of
authentic mauveine. Right: Mauveine made by Perkin’s method (oxidation
of aniline/o-toluidine/p-toluidine 25:50:25 or 37.5:37.5:25 or 33:33:33).
A larger scale synthesis from aromatic amine (4 g) (37.5:37.5:25) also
gave a dominant top spot (mauveine C). A number of TLC plates were run
as a check for reproducibility. The eluent was secBuOH:EtOAc:H2O:HOAc
(60:30:9.5:0.5).
greater in our starting materials. By oxidising a mixture of
N-tert-butyl-p-toluidine/o-toluidine/aniline with a greater ratio
of aniline present (1.0:1.5:2.0 or 1.0:1.5:2.5) TLC analysis
of the purified material showed the ratio of mauveine A 14 to
mauveine B 15 to have increased. Using approximately 1.8 equiv.
of aniline gave mauveine that by eye matched the A/B ratio of
authentic mauveine. Our TLC studies on the isolated products
from the oxidation of N-methyl-p-toluidine/o-toluidine/aniline
showed that as the ratio of o-toluidine/aniline was varied the
ratio of N-methyl mauveine A 6 to N-methyl mauveine B 7
also varied.18 More o-toluidine favours N-methyl mauveine B.
Purified mauveine made by Perkin’s method does not separate
into two resolved spots on a TLC plate. It separates into four
spots (Fig. 1) indicative of a more complex mixture of products.
This observation is similar to the results from the HPLC traces
published previously.14 The additional two spots presumably
contribute to a blue mauve shade of stained silk. In mauveine
made by Perkin’s method, note that mauveine B is quite a weak
TLC spot and, yet in authentic mauveine, mauveine B is a
stronger spot than mauveine A (see Fig. 1). This is one reason
why I am sceptical that Perkin made mauveine this way. The two
profiles are different and I have not been able to wash out the
extra chromophores. Heating and cooling a sample in water and
filtering, twice, still leaves a mixture of chromophores. Much
material is also lost. Other HPLC studies suggest that these
compounds are correctly assigned as mauveine A, B2, B and C.14
Since mauveine B2 and C have been characterised14 and contain
a 4-methylphenyl group at position 5, the synthesis of authentic
mauveine appears to lack any p-toluidine. If p-toluidine is
present it may compete with aniline to give 4-methylphenyl
rather than phenyl at the 5-position (Scheme 7), whereas N-tert-
butyl-p-toluidine does not.
NH
16
Scheme 6 Structure of N-tert-amyl-p-toluidine.
Silk dyeing
Silk dyeing and TLC analysis (secBuOH:EtOAc:H2O:HOAc
60:30:9.5:0.5) was done using a mauveine A/B mixture
prepared from the oxidation of pure N-tert-butyl-p-toluidine/
aniline/o-toluidine followed by de-tert-butylation of all the
product or from the de-tert-butylation of a pure mixture of
compounds 12 and 13. By TLC analysis the Rf values of
the two compounds 14 and 15 are the same as those of 1862
authentic mauveine and the slightly different shade of the two
spots on a TLC plate is very characteristic. The colour of silk
dyed with them is identical to that of silk dyed with authentic
mauveine. They were purified by chromatography eluting with
secBuOH/EtOAc/H2O/HOAc (60:30:9.5:0.5). Each product
or with both combined gives a brighter shade on silk than
the product obtained by elution from a column with cNH3/
MeOH (20:80). This is the first time that I have accurately
reproduced the shade of authentic mauveine on silk with a
mauveine chromophore (where R1 =H and an N-tolyl group
at position 3). In our hands, the oxidation of a mixture of
aromatic amines by Perkin’s method is lower yielding and more
complex. Methods for making mauveine by Perkin’s method
(generally referred to as the aqueous potassium dichromate/
H2SO4 oxidation of a mixture of aniline/o-toluidine/p-toluidine)
have been studied previously.16 Even after purification twice
by column chromatography, cNH3/MeOH (20:80) and then
secBuOH/EtOAc/H2O/HOAc (60:30:9.5:0.5), or by changing
the counterion to different anions such as chloride, bromide
and acetate and trituration with H2O, the material still stains
silk a blue shade of mauve that does not closely match the red
shade of 1862 authentic mauveine. Analysis by TLC of the
material prepared here showed it to contain less mauveine A
14 and more mauveine B 15 compared to authentic mauveine
probably because the ratio of o-toluidine/aniline oxidised was
It was also noted previously that oxidation of N-phenyl-p-
phenylenediamine and either pure aniline or pure o-toluidine
gave single characterisable chromophores, but when
a
mixture of aniline/o-toluidine (1.5:1.5) was used instead with
N-phenyl-p-phenylenediamine the reaction was a complex
mixture of mauveine chromophores from which no pure data
were obtained.16 This reaction should have given mauveine
C
25a (substituted at position 8 only with a methyl group). Hence
an N-alkyl group at position 3 helps to control the reaction
pathway.18
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JOURNAL OF CHEMICAL RESEARCH 2014 167
N
N
N
H2N
N
H
H2N
N
N
H
Mauveine B2 17
Mauveine C 18
Scheme 7 The structures of mauveine B2 and mauveine C.14
and filtered through a fine pore (4–8 μm porosity) sinter. The
precipitate was washed with H2O and then extracted with portions
of MeOH (40 mL×6) each time with agitation in the sinter. The
combined extracts were evaporated to dryness by heating in a beaker
on a hotplate. The product was purified by column chromatography on
silica gel. Elution with cNH3/MeOH (20:80) gave the title compound
(29.6 mg; 3.5%) as a dark solid, m.p.>220 °C. λmax (ethanol)/nm 552
(log ε 4.64) and 278 (4.61); νmax (diamond anvil) 3290(br), 1550(vs),
1402(vs), 1341(s), 1187(w), 1124(w), 1017(w) and 924(w); δH(400 MHz;
CD3OD) 1.15 (3H, t, J=7.1 Hz), 2.38 (3H, s), 3.76 (2H, q, J=7.1 Hz), 5.70
(1H, s), 5.99 (1H, s), 7.04 (2H, d, J=8.0 Hz), 7.26 (2H, d, J=8.3 Hz),
7.32–7.28 (2H, m), 7.42 (2H, d, J=7.6 Hz), 7.70–7.78 (3H, m) and 7.92
(2H, t, J= 8.1 H z); δC (100.1 MHz; CDCl3) 13.4, 22.0, 96.2, 97.2, 120.1,
125.0, 129.3, 129.8, 132.8, 132.9, 133.5, 134.9, 136.0, 137.1, 138.3,
138.7, 139.7, 140.4, 143.2, 156.4 and 161.5 (two peaks are missing); m/z
(Orbitrap ASAP) 405.2071 (M+, 100%) C27H25N4 requires 405.2074.
3-[4-Methylphenyl(isopropylamino)]-5-phenyl-7-aminophenazinium
sulfate (9): N-Isopropyl-p-toluidine hydrochloride (200 mg,
1.08 mmol) and aniline (300 mg, 3.23 mmol, 3.0 equiv.) were dissolved
in distilled H2O (200 mL) in a beaker acidified with cH2SO4 (six drops,
0.3 mL) followed by the addition of K2Cr2O7 (526 mg, 1.79 mmol,
1.67 equiv.). The mixture was stirred and heated at 70–80 °C for 4 h and
then cooled and filtered through a fine pore (4–8 μm porosity) sinter.
The precipitate was washed with H2O and then extracted with portions
of MeOH (40 mL×6), each time with agitation in the sinter. The
combined extracts were evaporated to dryness by heating in a beaker
on a hotplate. The product was purified by column chromatography on
silica gel. Elution with cNH3/MeOH (20:80) gave the title compound
(30.3 mg; 6.0%) as a dark solid, m.p.>220 °C. λmax (ethanol)/nm 550
(log ε 4.64) and 275 (4.61); νmax (diamond anvil) 2969(br), 1590(vs),
1550(s), 1505(s), 1471(vs), 1371(s), 1315(s), 1286(s), 1190(s), 1173(s),
1105(vs), 875(w), 829(s), 810(s), 793(s), 695(w), 619(w) and 600(w);
δH(400 MHz; CD3OD) 1.12 (6H, d, J=6.6 Hz), 2.39 (3H, s), 4.35 (1H, m),
5.50 (1H, s), 5.91 (1H, s), 6.91 (2H, d, J=8.1 Hz), 7.17 (2H, d, J=9.3 Hz),
7.25 (2H, d, J=7.8 Hz), 7.37 (2H, d, J=6.8 Hz), 7.71 (3H, m) and 7.81
(2H, d, J= 9.5 H z); δC (100.1 MHz; CDCl3) 21.2, 21.3, 51.4, 95.0, 96.7,
119.3, 123.5, 128.7, 130.9, 131.8, 132.5, 134.0, 135.1, 136.4, 137.2, 137.6,
137.8, 138.7, 138.9, 140.2, 156.4 and 160.0 (one peak is missing); m/z
(Orbitrap ASAP) 419.2226 (M+, 100%) C28H27N4 requires 419.2230.
Attempted oxidation of 3-[4-methylphenyl(isopropylamino)]-
Conclusion
Mauveine A 14 and mauveine B 15 have been prepared by the
oxidation of a mixture of pure N-tert-butyl-p-toluidine/aniline/
o-toluidine followed by the acid-catalysed removal of the tert-
butyl group. They stain silk a red mauve shade, which matches
that of silk stained with Perkins 1862 authentic mauveine.
The chromophores can be separated or left combined. The
mauveine chromophore C25b 11 stains silk a blue shade of mauve
showing how the shade is finely adjusted by the methyl group
substituents. This chromophore was not present in our mixture
of mauveine A 14 and mauveine B 15 which will enhance the
red shade of mauve on silk. The yield is lower for the oxidation
of N-tert-butyl-p-toluidine/aniline/o-toluidine compared to the
yield for the oxidation of N-isopropyl-p-toluidine/aniline/o-
toluidine. The steric hindrance of the tert-butyl group appears
to hinder the reaction but the yield is still higher and the product
purer than that obtained for the oxidation of mixtures of aniline/
o-toluidine/p-toluidine. An N-alkyl group at position 3 favours
a selective reaction pathway to mauveine A and mauveine B
derivatives. Our studies suggest that Perkin’s synthesis of
mauveine lacked any p-toluidine but used an N-alkylated
p-toluidine instead that was subsequently deprotected in the
product. The tert-butyl group is one such example of a traceless
substituent that is stable in the mauveine synthesis but can be
removed.
Experimental
IR spectra were recorded on an ATI Mattson FTIR spectrometer
using potassium bromide discs. UV spectra were recorded using a
PerkinElmer Lambda 25 UV-VIS spectrometer with EtOH as the
solvent. 1H and 13C NMR spectra were recorded at 400 MHz and
100.5 MHz respectively using a Varian 400 spectrometer. Chemical
shift values, δ, are given in ppm by reference to the residual solvent
and coupling constants, J are given in Hz. Low resolution and high
resolution mass spectra were obtained at the University of Wales,
Swansea using electron impact ionisation and chemical ionisation.
Melting points were determined on a Kofler hot-stage microscope.
N-Methyl,18 N-ethyl and N-isopropyl-p-toluidines were commercially
available. The solvent mixture secBuOH:EtOAc:H2O:HOAc
(60:30:9.5:0.5) was used for column chromatography to get high
grade mauveine for comparison with authentic mauveine dyed on
silk. The solvent mixture cNH3/MeOH (20:80) was used to purify
crude reaction mixtures. Silk strips were cut from a gentleman’s
handkerchief and silk dyeing was done from hot water with stirring.
The preparation of N-tert-butyl-p-toluidine by heating p-toluidine
5-phenyl-7-aminophenazinium sulfate (9): Compound
9 (8 mg,
0.0171 mmol) in H2O (100 mL) acidified with cH2SO4 (0.5 mL,
10 drops) was heated to 50–60 °C and treated with K2Cr2O7 (15 mg,
0.051 mmol) for 15 min. A precipitate quickly formed which was
filtered off after cooling. The filtrate was treated with base to
precipitate any remaining chromophore but very little was present. The
first precipitate was shown by 1H NMR to be identical with the starting
material and also had the same Rf value.
3-[4-Methylphenyl(amino)]-5-phenyl-7-aminophenazinium
sulfate (11) and 3-[4-methylphenyl(tert-butylamino)]-5-phenyl-
7-aminophenazinium sulfate (10) Method 1: Standard procedure:
p-Toluidine hydrochloride (266 mg, 1.87 mmol) and tert-butanol
(3 mL) were sealed in a 23 mL PTFE lined Parr digestion bomb and
heated at 150 °C for 24 h. After cooling the mixture was added to
distilled H2O (200 mL) containing cH2SO4 (six drops, 0.3 mL) and
aniline (520 mg, 5.6 mmol) followed by the addition of K2Cr2O7
t
HCl in BuOH for less than 24 h leaves some unreacted p-toluidine
detectable by TLC. An increased quantity of non-tertiary butylated
chromophores form in the product upon oxidation when mixed with
aromatic amines.
3-[4-Methylphenyl(ethylamino)]-5-phenyl-7-aminophenazinium
sulfate (8): N-Ethyl-p-toluidine (250 mg, 1.85 mmol) and aniline
(517 mg, 5.55 mmol, 3.0 equiv.) were dissolved in distilled H2O
(200 mL) in a beaker and acidified with cH2SO4 (six drops, 0.3 mL)
followed by the addition of K2Cr2O7 (909 mg, 3.1 mmol, 1.67 equiv.).
The mixture was stirred and heated at 70–80 °C for 4 h then cooled
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168 JOURNAL OF CHEMICAL RESEARCH 2014
(916 mg, 3.1 mmol, 1.67 equiv.). The mixture was stirred and heated
at 70–80 °C for 5 h then cooled and filtered through a fine pore
(4–8 μm porosity) sinter. The precipitate was washed with H2O and
then extracted with portions of MeOH (40 mL×6), each time with
agitation in the sinter. The combined extracts were evaporated to
dryness by heating in a beaker on a hotplate. The product was purified
by chromatography on silica gel. Elution with cNH3/MeOH (20:80)
gave the first title compound (3 mg, 0.4%) as a dark solid, m.p.>220 °C.
λmax (ethanol)/nm 554 (log ε 4.7) and 282 (4.6); νmax (KBr) 3427(br),
1596(s), 1530(w), 1504(s), 1476(s), 1384(s), 1318(s), 1173(s) and 1134(s);
δH(400 MHz; CD3OD) 2.29 (3H, s), 6.00(1H, s), 6.28 (1H, s), 7.02
(2H, d, J=8.2 Hz), 7.10 (2H, d, J=8.2 Hz), 7.85 (1H, d, J=9.0), 7.41
(1H, d, J=9.0 Hz), 7.50 (2H, d, J=7.3 Hz), 7.75 (1H, d, J=7 Hz), 7.81
(2H, t, J=7.8 Hz), 7.93 (1H, d, J=8.8 Hz) and 7.9 (1H, d, J=9.6 Hz);
δC(100.1 MHz; CDCl3) 19.5, 93.5, 93.6, 121.7, 122.0, 127.4, 129.2, 129.6,
130.7, 131.2, 133.2, 133.9, 135.5, 135.8, 136.3, 136.3, 136.8, 137.4, 137.4,
153.0 and 158.1; m/z (Orbitrap ASAP) 377.1760 (M+, 100%) C25H21N4
requires 377.1761. This was followed by the second title compound
(9 mg, 1%) as a dark solid, m.p.>220 °C. λmax 550 (log ε 4.6) and 280
(4.5); νmax (KBr) 3144(br), 1597(vs), 1533(s), 1487(vs), 1400(vs),
1345(s), 1313(vs), 1110(vs), 874(w), 815(w) and 618(w); δH(400 MHz;
CD3OD) 1.36 (9H, s), 2.41 (3H, s), 5.95 (1H, s), 6.02 (1H, s), 6.94 (2H, d,
J=7.0 Hz), 7.10 (1H, d, J=9.0 Hz), 7.26 (2H, d, J=7.0 Hz), 7.30 (1H, d,
J=9.0 Hz), 7.47 (2H, d, J=5.0 Hz), 7.80 (4H, m), 7.90 (1H, d, J=9.0 Hz);
δC(100.1 MHz; CDCl3) 19.8, 28.8, 58.8, 93.4, 98.6, 121.6, 121.9, 127.5,
129.3, 130.4, 130.7, 131.2, 131.3, 133.8, 134.8, 135.0, 136.4, 137.4, 137.7,
138.5, 140.3, 154.9 and 158.2; m/z (Orbitrap ASAP) 433.2383 (M+,
100%) and 377.1759 (52) C29H29N4 requires 433.2387 and fragment
C25H21N4 requires 377.1761.
A TLC plate run with the same eluent is similar to that of authentic
mauveine. Increasing the ratio of aniline from 1.5 to 2.0 to 2.5 equiv.
increases the quantity of mauveine A formed.
Mauveine A (14) and mauveine B (15) Method 2: A sample of N-tert-
butyl-p-toluidine 421 was made by method 1. The crude reaction
mixture was diluted with 2M KOH, extracted with DCM (30 mL) and
then the DCM layer was washed with H2O. This layer was concentrated
under reduced pressure and purified by chromatography on silica gel,
rather than by distillation. Elution with Et2O/light petroleum 40–60
(25:75) gave N-tert-butyl-p-toluidine 4 (100 mg, 0.61 mmol) with
identical spectroscopic properties to literature material. Oxidation
by method 1 followed by chromatography on silica gel gave a mixture
of the tert-butyl-substituted derivatives of mauveine A 12 and B 13
(20 mg, 7%) and de-tert-butylation gave a mixture of the above title
compounds (14 mg, 5%) with the same spectroscopic properties
to the material from the previous synthesis. A trace of de-tert-
butylated material that formed in the reaction, which elutes first and
has a different shade, was combined with the tert-butylated material
so that all of the chromophore was treated with acid. After de-tert-
butylation with acid method 1 was followed to purify the products.
After oxidation and filtration the tert-butyl-substituted products were
extracted more easily from the precipitate to give clear washings with
MeOH (40 mL×4).
Attempted synthesis of N-tert-amyl-p-toluidine (16): p-Toluidine
hydrochloride (266 mg, 1.87 mmol) and tert-amyl-alcohol (3 mL) were
sealed in a 23 mL PTFE lined Parr digestion bomb and heated at 150 °C
for 24 h. After cooling the reaction mixture was diluted with 2M KOH
and extracted with DCM (30 mL). This layer was dried over MgSO4 then
concentrated under reduced pressure and purified by chromatography
on silica gel. Elution with Et2O/light petroleum 40–60 (25:75) gave the
starting material p-toluidine (148 mg, 74%) identified by comparison of
its Rf value to authentic material and by 1H NMR spectroscopy.
3-[4-Methylphenyl(amino)]-5-phenyl-7-aminophenazinium sulfate
(11): Compound 10 (9 mg, 0.019 mmol) was added to a mixture of
MeOH (10 mL) and treated with cHCl (5 mL). After heating for 1 h
the mixture was evaporated to dryness in a beaker. MeOH (30 mL)
was added and it was purified by chromatography on silica gel. cNH3/
MeOH (20:80) eluted the title compound 11 (6 mg, 74%) with the same
spectroscopic data as compound 11 above. Total combined yield of
compound 11 (9 mg, 1.1%).
This work, in part, was completed by the author at the
Department of Chemistry, University of Malaya, Faculty of
Science, Kuala Lumpur, 50603, Malaysia.
I am grateful to the EPSRC national mass spectrometry
service centre for mass spectra and to the Manchester Museum
of Science and Industry (MoSI) and the trustees for providing a
sample of authentic mauveine (or archived mauveine).
1-Methyl-3-[4-methylphenyl(amino)]-5-phenyl-7-amino-8-
methylphenazinium sulfate (15) (mauveine B) and 3-[4-methylphenyl
(amino)]-5-phenyl-7-amino-8-methylphenazinium sulfate (14)
(mauveine A): These were made by method 1 following the standard
procedure except that aniline was replaced by a mixture of aniline
(261 mg, 0.0028 mmol, 1.5 equiv.) and o-toluidine (300 mg,
0.0028 mmol, 1.5 equiv.). The combined methanol extracts were heated
to dryness and purified by chromatography on silica gel. Elution with
cNH3/MeOH (20:80) gave a mixture of the tert-butyl-substituted
derivatives of the title compounds (73 mg, 8.0%). Some deprotected
material, with a different shade, elutes first and was separated at
this stage. The title compounds were deprotected by warming with a
mixture of cHCl (5 mL) and MeOH (10 mL) for 1 h and evaporating to
dryness. The crude product was then re-purified by chromatography
on silica gel. Elution with cNH3/MeOH (20:80) gave a mixture which
was then purified again by chromatography on silica gel. Elution
with secBuOH:EtOAc:H2O:HOAc (60:30:9.5:0.5) gave the title
compound mauveine B (31 mg, 3.5%) as a dark solid, m.p.>220 °C
followed by the title compound mauveine A (11 mg, 1.3%) as a dark
solid, m.p.>220 °C which were both identified by comparison of
their spectroscopic data (1H NMR, accurate mass spectrum, Rf value
and colour of dyed silk) with authentic material.11,14 The intermediate
mixture of tert-butyl-substituted chromophores 12 and 13 were
isolated but not separated. Data for mauveine B 15: δH(400 MHz;
CD3OD) 2.29 (3H, s), 2.32 (3H, s), 2.78 (3H, s), 6.08 (1H, s), 6.17 (1H,
s), 7.00 (2H, d, J=8.0 Hz), 7.10 (2H, d, J=8.0 Hz), 7.27 (1H, s), 7.48
(2H, d, J=8.0 Hz), 7.76–7.80 (3H, m) and 7.89 (1H, s); m/z (Orbitrap
ASAP) 405.2073 (M+, 100%) C27H25N4 requires 405.2074; 419.2227
(10) C28H27N4 requires 419.222; data for mauveine A 14: δH(400 MHz;
CD3OD) 2.30 (3H, s), 2.38 (3H, s), 6.12 (1H, s), 6.33 (1H, s), 7.03 (2H,
d, J=7.0), 7.11 (2H, d, J=7.0 Hz), 7.42 (1H, d, J=9.6 Hz), 7.51 (2H, d,
J=7.0 Hz), 7.74–7.84 (3H, m), 7.87 (1H, s) and 8.01 (1H, d, J=9.6 Hz);
m/z (Orbitrap ASAP) 391.1918 (M+, 100%) C26H23N4 requires 391.1917.
Received 4 December 2013; accepted 11 January 2014
Paper 1302325 doi: 10.3184/174751914X13912601347455
Published online: 7 March 2014
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