Exothermic thermal reaction of dopamine with 3,5-dinitrobenzoic acid

Article abstract of DOI:10.1002/poc.669

Pyrolysis of the crystalline 1:1 molecular complex DA·dnba, which was prepared from cocrystallization of dopamine (DA) and 3,5-dinitrobenzoic acid (dnba), was studied. This cocrystal decomposed violently at the melting-point, leading to the formation of a black solid along with a tiny amount of 3-amino-5-nitrobenzoic acid (1). The pyrolysis reaction was followed by differential scanning calorimetry (DSC) and one large exothermic peak was observed at the decomposition temperature. In view of the DSC patterns for cocrystal DA·dnba and other compounds, it seems that both a catechol moiety and an amino group of DA in addition to a strong electron acceptor such as dnba are required for the appearance of the exothermic peak. On the basis of (a) elemental analysis of the black solid and (b) other pyrolysis experiments for cocrystals PA·dnba (PA: β-phenylethylamine), BA·dnba (BA: benzylamine), DMDA·dnba (DMDA: O,O′-dimethyldopamine) and DHBA·dnba (DHBA: 3,4-dihydroxybenzylamine), it is assumed that the black solid was formed mainly through elimination of more than one molecule of water from one molecule of DA·dnba. Copyright

Full text of DOI:10.1002/poc.669

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2003; 16: 849–857
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.669
Exothermic thermal reaction of dopamine with
3,5-dinitrobenzoic acid
Yoshikatsu Ito* and Satoru Arimoto
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 606-8501, Japan
Received 19 January 2003; revised 14 March 2003; accepted 10 April 2003
ABSTRACT: Pyrolysis of the crystalline 1 : 1 molecular complex DAꢀ dnba, which was prepared from cocrystalliza-
tion of dopamine (DA) and 3,5-dinitrobenzoic acid (dnba), was studied. This cocrystal decomposed violently at the
melting-point, leading to the formation of a black solid along with a tiny amount of 3-amino-5-nitrobenzoic acid (1).
The pyrolysis reaction was followed by differential scanning calorimetry (DSC) and one large exothermic peak was
observed at the decomposition temperature. In view of the DSC patterns for cocrystal DAꢀ dnba and other
compounds, it seems that both a catechol moiety and an amino group of DA in addition to a strong electron acceptor
such as dnba are required for the appearance of the exothermic peak. On the basis of (a) elemental analysis of the
black solid and (b) other pyrolysis experiments for cocrystals PAꢀ dnba (PA: ꢀ-phenylethylamine), BAꢀ dnba (BA:
benzylamine), DMDAꢀ dnba (DMDA: O,O0-dimethyldopamine) and DHBAꢀ dnba (DHBA: 3,4-dihydroxybenzyla-
mine), it is assumed that the black solid was formed mainly through elimination of more than one molecule of water
from one molecule of DAꢀ dnba. Copyright # 2003 John Wiley & Sons, Ltd.
KEYWORDS: dopamine; 3,5-dinitrobenzoic acid; pyrolysis; differential scanning calorimetry; cocrystal
INTRODUCTION
In the course of our study on the photochemistry of two-
component crystals,9 we were interested in the oxidation
of catecholamines. We have found that dopamine (DA)
and its analogs, homoveratrylamine (O,O0-dimethyldopa-
mine, DMDA) and tyramine (TA), are able to form a 1 : 1
crystalline molecular complex with suitable electron ac-
ceptors such as 3,5-dinitrobenzoic acid (dnba), 3-nitro-
benzoic acid and picric acid (pic). Thermal analysis of the
crystalline complexes DAꢀ dnba and DAꢀpic by differen-
tial scanning calorimetry (DSC) has revealed a lerge
exothermic peak near the melting-points and black mate-
rials have resulted. As will be described in this paper, we
investigated these thermal reactions in some detail, be-
cause the chemical structures of all the black–brown
materials (melanin, humus, etc.) that were formed from
oxidation of catechols6–8 are as yet unknown.
Because dopamine (DA) is an important neurotransmitter
in the brain,1,2 its chemical reactivity has an inherent
interest. For example, it reacts with an aldehyde to form a
tetrahydroisoquinoline (Pictet–Spengler condensation).3
This reaction and also N-acylation of a ꢀ-phenylethyla-
mine followed by cyclization into a 3,4-dihydroisoquino-
line (Bischler–Napieralski cyclization)4 are important
reactions in the syntheses of isoquinoline alkaloids.5
The best known reactivity of dopamine is its vulnerability
to oxidation. DA is easily autoxidized in neutral or alka-
line solution to furnish a black polymer called melanin via
a series of intermediates such as semiquinone and qui-
none.6 On the other hand, DA is stable to oxidation under
acidic conditions. In fact, since dopamine is difficult to
isolate as the free amine under air, it is distributed com-
mercially as a salt with hydrochloric acid (DAꢀ HCl)
or hydrobromic acid (DAꢀ HBr). Enzymatic or non-enzy-
matic oxidation of catechols giving rise to melanin or
tanned materials is ubiquitous in the animal, plant and
fungi kingdoms.7 Also, oxidative polymerization of phe-
nolic compounds leading to dark-colored humic sub-
stances is an important reaction in soil.8
RESULTS AND DISCUSSION
All the crystalline molecular complexes listed in Table 1
were obtained by cocrystallization of the amine and the
acceptor from suitable solvents (all the cocrystals shown
in Table 1 were photoinert in the solid state under similar
irradiation conditions to those described previously.9)
Their melting-points are summarized in Table 2. X-ray
crystallographic analyses of cocrystals DAꢀ dnba,10
DMDAꢀ dnba,11 DMDAꢀpic (S. Ohba and Y. Ito, unpub-
lished result), and TAꢀpic12 have already been carried out
*Correspondence to: Y. Ito, Department of Synthetic Chemistry and
Biological Chemistry, Graduate School of Engineering, Kyoto Uni-
versity, Kyoto 606-8501, Japan.
E-mail: yito@sbchem.kyoto-u.ac.jp
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850
Y. ITO AND S. ARIMOTO
Table 1. Formation of crystalline molecular complexes of
catecholamines (B) with electron acceptors (A)
Table 2. Solvents for cocrystallization and melting-points of
cocrystals
A
Cocrystallization
solvent
Cocrystal
M.p. ( ꢁC)
DAꢀ dnba
DAꢀpic
EtOH–H2O
MeOH–H2O
EtOH–MeOH
EtOH
EtOH–H2O
MeOH–H2O
MeOH
221–229 (decomp.)
209–216 (decomp.)a
195–199
DMDAꢀ dnba
DMDAꢀpic
TAꢀ dnba
172–175b
B
226–234
205–207
166–172
186–190
191–193 (decomp.)
TAꢀpic
PAꢀ dnbac
BAꢀ dnbac
DHBAꢀ dnbac
EtOH–MeOH
MeOH–H2O
a
Lit. 17m.p. 189–190 ꢁC (decomp.).
Lit. 18m.p. 164–166 ꢁC.
PA, ꢀ-phenylethylamine; BA, benzylamine; DHBA, 3,4-dihydroxyben-
b
c
zylamine.
reactions were followed by DSC. As can be seen from
Figs 1(a) and 2(a), both DAꢀ dnba and DAꢀpic, upon
heating, first showed an endothermic peak due to melting.
This was suddenly replaced by a large exothermic peak,
indicating the occurrence of certain violent chemical
reactions. In contrast, cocrystals of DMDAꢀ dnba or
DMDAꢀpic showed only an endotherm due to melting
[Figs 1(b) and 2(b), respectively]. It should be noted that
DAꢀ HCl [lit.14 m.p., 241 ꢁC (decomp.)] also showed only
an endothermic peak at the melting-point [Fig. 1(c)],
suggesting no accompanying drastic reactions.
A typical experiment for the thermal reaction of
DAꢀ dnba is as follows. Cocrystals of DAꢀ dnba were
crushed in an agate mortar and 222 mg were heated on a
hot-plate (250 ꢁC). The sample turned brown–black with
melting and concomitant bubbling, and after 10 min the
whole mass changed into a black solid. Heating was
continued for additional 4.8 h. The reaction mixture was
washed with hot MeOH several times (10 ml ꢂ 9) to give
and their amine component was found to exist as the
ammonium salt like that in dopamine hydrochloride,
DAꢀ HCl.13 The DA molecule in the DAꢀ dnba cocrystal
was stable to autoxidation for an indefinite time, as in
DAꢀ HCl.
Heating cocrystals of DAꢀ dnba or DAꢀpic on a hot-
plate resulted in the sudden decomposition of the crystal
when the plate temperature reached near the melting-point
of the sample, giving a black pigment along with a small
amount of 3-amino-5-nitrobenzoic acid (1) or picramic
acid (2) [reactions (1) and (2) in Scheme 1]. These thermal
Scheme 1. Pyrolysis of DAꢀ dnba, DAꢀ pic, and a 1:1:1 mixture of DAꢀ HCl, NaOH and dnba
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EXOTHERMIC REACTION OF DOPAMINE WITH 3,5-DINITROBENZOIC ACID
851
Figure 1. DSC traces for (a) DAꢀ dnba, (b) DMDAꢀ dnba, (c) DAꢀ HCl and (d) a 1 : 1: 1 mixture of DAꢀ HCl, NaOH and dnba
Figure 2. DSC traces for (a) DAꢀ pic, (b) DMDAꢀ pic, (c) PAꢀ dnba and (d) dnba
a black residue (180 mg, 81 wt%). From the MeOH wash-
ing, 3-amino-5-nitrobenzoic acid (1) was obtained in a
small quantity (1 mg, ꢃ1%). In a separate pyrolysis ex-
periment employing an equimolar mixture of DAꢀ HCl,
NaOH, and dnba [reaction (3) in Scheme 1], 1 was
produced in a much higher yield (21%) and was isolated
by PTLC, followed by HPLC (see below).
In order to obtain some structural information, the
black residue was subjected to measurements by powder
1
x-ray diffraction (PXD), IR (in KBr), H NMR (in D2O
containing 5% NaOD), UV/Vis (in 1 M NaOH), FAB-MS
(in 1 M NaOH or DMF) and elemental analysis. The PXD
pattern [Fig. 3(A)] and the IR spectrum [Fig. 3(B)] are
broad, but the IR absorption attributable to the nitro group
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852
Y. ITO AND S. ARIMOTO
1
solvent used, the H NMR, UV/Vis and FAB-MS (not
shown) spectra do not reflect the property of the entire
1
sample. The broad nature of the PXD, IR and H NMR
spectra and the low solubility in all kinds of solvents
suggest that the black material is polymeric.
The analytical data for the black solid [H, 2.74; C,
57.88; N, 13.23; (O, 26.15)%] is in fair agreement with
the empirical formula C15H9N3O5: H, 2.92; C, 57.88; N,
13.50; O, 25.70%. The black solid that was obtained
from a different pyrolysis experiment afforded nearly the
same analytical data, confirming its reproducibility. The
empirical formula C15H9N3O5 suggests that three mole-
cules of H2O are eliminated from the thermal decom-
position of one molecule of DAꢀ dnba. The black pigment
obtained from DAꢀpic [reaction (2) in Scheme 1] was
analyzed as C 53.09, H 2.16, N 15.59%. These analytical
data can be approximated by the elemental composition
C14H6.5N3.5 O6, which requires C 52.59, H 2.05, N
15.33%, i.e. by (dopamine)1(picric acid)1-3 H2O-0.5 NH3.
For comparison with the pyrolysis of cocrystal
DAꢀ dnba, pyrolysis of an equimolar mixture of
DAꢀ HCl, NaOH and dnba was carried out (reaction 3
in Scheme 1). A black solid (m.p.>300 ꢁC), whose IR
spectrum was very similar to that shown in Fig. 3(B), was
obtained. However, the yield of the black solid was much
lower (29 vs 81 wt%) and the elemental analysis was
considerably different (H, 3.37; C, 56.71; N, 10.96% vs
H, 2.74; C, 57.88; N, 13.23%). Furthermore, the yield of
1 was much higher (21% vs 1%), and the peak width of
the DSC exotherm was much broader [Fig. 1(d) vs Fig.
1(a)]. Considering this difference in the DSC patterns, the
crystal structure of the cocrystal DAꢀ dnba may possibly
Figure 3. (A) Powder x-ray diffraction pattern and (B) IR
spectrum (in a KBr disc) for the black pigment
1
is clearly visible at 1530 and 1345 cmꢄ1. The H NMR
(not shown) and UV/Vis (not shown) spectra are also very
broad. However, because of the low solubility in the
Figure 4. DSC traces for (a) a 1 : 1 mixture of DAꢀ HCl and NaOH, (b) a 1 : 1 : 1 mixture of DAꢀ HCl, NaOH and dnbn, (c)
catechol and (d) a 1 : 1 mixture of catechol and dnba
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EXOTHERMIC REACTION OF DOPAMINE WITH 3,5-DINITROBENZOIC ACID
853
like cyclization (e.g. 3a ! 4a) and dehydrative polymer-
ization of the catechol moiety.
In order to support Scheme 2, the experiments sum-
marized in Schemes 3 and 4 were carried out. Thus,
short-time pyrolyses of cocrystals PAꢀ dnba (PA:
Scheme 2. A tentative scheme showing the formation of
one possible structure for the balck pigment that was
produced from pyrolysis of cocrystal DAꢀ dnba
be more or less favorable for the exothermic thermal
reaction to occur (see below).
Thermal analyses of a 1 : 1 mixture of DAꢀ HCl and
NaOH, a 1 : 1 : 1 mixture of DAꢀ HCl, NaOH and 3,5-
dinitrobenzonitrile (dnbn), catechol, and a 1 : 1 mixture
of catechol and dnba (Fig. 4) were also performed. Only
a 1 : 1 : 1 mixture of DAꢀ HCl, NaOH and dnbn exhibited
an exotherm [Fig. 4(b)]. Therefore, it seems in view of the
above thermal analyses (Figs 1, 2 and 4) that both a
catechol moiety and an amino group of DA in addition to
a strong electron acceptor such as dnba, pic and dnbn are
required for the appearance of an exothermic peak.
Compounds 3a, DHBAꢀ dnba and 6 showed an exother-
mic DSC peak, whereas 5, BAꢀ dnba, and 7 displayed
only an endothermic peak. We are planning further
thermochemical studies, including thermogravimetry.
As mentioned earlier, the elemental analysis of the
black solid suggests that three molecules of H2O are
eliminated from the thermal decomposition of one mo-
lecule of DAꢀ dnba. Although it may be too early to do so,
Scheme 2 is presented as a tentative mechanism for the
formation of the black solid. The mechanism involves the
competing occurrence of three dehydration steps: amide
formation (e.g. DAꢀ dnba ! 3a), a Bishler–Napieralski-
Scheme 3. Short-time pyrolysis of DAꢀ dnba and other
related cocrystals PAꢀ dnba, DHBAꢀ dnba, BAꢀ dnba and
DMDAꢀ dnba
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854
Y. ITO AND S. ARIMOTO
We have no very strong evidence for the formation of
the dihydroisoquinoline ring. However, pyrolysis of
DMDAꢀ dnba formed a 3,4-dihydroisoquinoline (4b),
albeit in a trace quantity (0.5%, Scheme 3). Furthermore,
the FAB mass spectra of the black solid, which were
measured under several different conditions, always dis-
played a peak at m/z 329. These findings are consistent
with the formation of the ring structure for 1-(3,5-dini-
trophenyl)-6,7-dihydroxy-3,4-dihydroisoquinoline (4a)
(m/z 329) upon pyrolysis of DAꢀ dnba. It is known that
the Bishler–Napieralski cyclization is promoted by
substituting electron-releasing groups (e.g. OMe) on the
ꢀ-phenethyl aryl ring.4
As stated above, production of 3-amino-5-nitrobenzoic
acid (1) is a very minor reaction in the pyrolysis of
DAꢀ dnba (Scheme 1). Indeed, regardless of the pyrolysis
ꢁ
time (ꢃ0.1–5 h at a hot-plate temperature of 250 C), the
yield of 1 was constantly low (ꢃ1%). Interestingly,
reduction of nitro-aromatics into amino-aromatics by
the reaction with phenols or humic monomers and poly-
merization of catechols leading to humic substances are
important reactions in the environment or in soil.8,15 Two
possible modes for the catechol polymerization were
considered to occur [see structures (a) and (b)]. Both
modes are oxidative polymerization and are different
from the dehydrative polymerization mode assumed in
Scheme 2. It is likely that in the case of the pyrolysis of an
equimolar mixture of DAꢀ HCl, NaOH and dnba, the
oxidative polymerization had substantially taken place,
since the yield of 1 was much higher (21%). In the
production of 1, the nitro group of dnba was presumably
reduced by the catechol and amino groups of DA.
Scheme 4. Preparation and short-time pyrolysis of the
relevant amides 3a, 5, 6 and 7
ꢀ-phenylethylamine), BAꢀ dnba (BA: benzylamine), and
DMDAꢀ dnba furnished the amides 5, 7 and 3b in reason-
able yields (7, 11 and 14%, respectively), while similar
short-time pyrolyses of cocrystals DAꢀ dnba and
DHBAꢀ dnba (DHBA: 3,4-dihydroxybenzylamine) did
not afford detectable amounts of the corresponding amides
3a and 6 (Scheme 3). In the latter cases, only black solids
were obtained. The unsuccessful detection of 3a and 6 is
probably due to their rapid thermal decomposition, beca-
usethey contain areactivecatecholsysteminthemolecule.
In fact, the amides 3a and 6 were prepared by an alternative
method using 3,5-dinitrobenzoyl chloride and the amine,
and these amides were found to be easily converted to
black materials by short-time pyrolysis (Scheme 4). As a
result, the amide formation upon pyrolysis of DAꢀ dnba
appears to be a true event. In addition, these pyrolysis
data indicate that a catechol moiety is necessary for the
production of a black pigment, since all the compounds
having this moiety (DAꢀ dnba, DHBAꢀ dnba, 3a and 6)
produced one (see Schemes 3 and 4).
X-ray crystallographic analyses of cocrystals
DAꢀ dnba,10 DMDAꢀ dnba,11 PAꢀ dnba (S. Arimoto and
Y. Ito, unpublished result), and DAꢀ HCl13 have already
been carried out. [Incidentally, we would like to mention
that the solid-state conformation of the ꢀ-phenylethyla-
mine component is gauche perpendicular for DAꢀ dnba,
DMDAꢀ dnba, DMDAꢀpic (S. Ohba and Y. Ito, unpub-
lished result), and TAꢀpic,12 whereas it is anti perpendi-
cular for DAꢀ HCl13 and PAꢀ dnba. At the binding site of
dopamine receptors D1 and D2, DA is assumed to take a
trans coplanar conformation,16 which is different from
that observed in the crystal]. The shortest intermolecular
distance between the ammonium nitrogen and the neigh-
˚
˚
boring carboxylate carbon is 3.38 A for DAꢀ dnba, 3.50 A
˚
for DMDAꢀ dnba, and 3.51 A for PAꢀ dnba. The shortest
intermolecular distance between the catechol oxygen is
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EXOTHERMIC REACTION OF DOPAMINE WITH 3,5-DINITROBENZOIC ACID
Table 3. Analytical data for cocrystalsa
855
Calc (%)
H
Found (%)
H
C
N
C
N
DAꢀ dnba
DAꢀpicb
49.32
40.20
51.91
46.83
51.58
45.91
54.05
52.67
46.79
4.14
4.34
4.87
4.42
4.33
3.85
4.54
4.10
3.90
11.50
13.39
10.68
13.65
12.03
15.30
12.61
13.16
11.69
49.23
40.46
51.67
47.07
51.54
45.85
54.09
52.77
47.09
4.06
4.15
4.81
4.47
4.26
3.78
4.67
4.26
3.94
11.47
13.69
10.69
13.35
12.08
15.33
12.61
13.14
11.31
DMDAꢀ dnba
DMDAꢀpic
TAꢀ dnba
TAꢀpic
PAꢀ dnba
BAꢀ dnba
DHBAꢀ dnbab
a
All the cocrystals, except DAꢀpic and DHBAꢀ dnba, gave satisfactory C, H and N analyses (within ꢅ 0.3%) as (amine)1(nitro compound)1.
Cocrystals DAꢀpic and DHBAꢀ dnba contained water in the crystal: (DA)1(pic)1(H2O)2 and (DHBA)1(dnba)1(H2O)0.45.
b
˚
˚
˚
diffractometer using Cu Kꢁ radiation (1.5406 A). For
4.65 A for DAꢀ dnba and 4.83 A for DAꢀ HCl. The fact
that both intermolecular atomic distances are shortest for
DAꢀ dnba is compatible with the present result that
DAꢀ dnba has the highest thermal reactivity among these
four cocrystals, since only DAꢀ dnba displayed an
exothermic DSC peak (Figs 1 and 2). Because of melting
or disruption of the crystal structure, however, it is not
clear to what extent the crystal structure controls the
thermal reactivity of these crystals.
pyrolysis, the sample was placed in a 100 ml Erlenmeyer
flask equipped with a water-cooled condenser and heated
on a Barnstead hot-plate (Thermolyne Type 1900).
Materials
All the compounds used for preparation of cocrystals
were purchased commercially. 3-Amino-5-nitrobenzoic
acid (1) and picramic acid (2) were also commercially
available.
CONCLUSIONS
The cocrystal between dopamine and 3,5-dinitrobenzoic
acid DAꢀ dnba underwent a violent thermal reaction,
giving a black solid. From inspection of the DSC patterns
for DAꢀ dnba and other compounds (Figs 1, 2 and 4), it
was indicated that both a catechol moiety and an amino
group of DA in addition to a strong electron acceptor such
as dnba, picric acid (pic) and 3,5-dinitrobenzonitrile
(dnbn) are required for appearance of an exothermic
peak. Probably, the black solid was formed mainly from
multiple dehydration reactions. Evidently, further studies
such as thermogravimetric analysis and more structural
elucidation of the black solid are needed to establish the
mechanisms of the present thermal reactions of dopamine
with electron acceptors.
Cocrystallization9
The solvents for cocrystallization, the melting-points of
cocrystals and their analytical data are summarized in
Tables 2 and 3. 1H NMR spectra (in DMSO-d6) of all the
cocrystals were essentially a simple sum of the spectra of
their components, confirming that the molar ratio of the
corresponding amine and the nitro compound was 1 : 1 in
the cocrystal. The IR spectra (in KBr) of the cocrystals
were definitely different from the superposition of the
spectra of the components. For example, the IR frequency
for the CO2H group of dnba at 1703 cmꢄ1 is missing in
all the dnba cocrystals.
ꢀ
DA dnba. A hot solution containing 1.188 g (5.03 mmol)
EXPERIMENTAL
of dopamine hydrobromide (DAꢀ HBr) in EtOH (10 ml)
was mixed with a hot solution containing 1.087g
(5.02mmol) of 3,5-dinitrobenzoic acid (dnba) in EtOH
(6ml), then 5.0 ml of 1 M NaOH solution were added. The
mixture was filtered and the filtrate was left for 2 days at
room temperature. Orange prisms appeared and these
were collected by filtration and in vacuo at room
temperature. Yield, 1.36 g (60%); m.p. 221–229 ꢁC (de-
comp.).
General procedures
DSC traces were recorded on a Shimadzu DSC-60
calorimeter at a scanning rate of 10 ꢁC minꢄ1. DSC exp-
eriments were performed under a nitrogen atmosphere.
1
IR, H NMR, MS and UV/Vis spectra were measured
with Shimadzu FTIR-8100A, JEOL EX-270J, JEOL
JMS-HX 110A and Shimadzu UV-2400PC spectro-
meters, respectively. Powder x-ray diffraction (PXD)
patterns were obtained with a MAC Science MX Labo
ꢀ
DA pic. A hot solution containing 964 mg (4.98 mmol)
of dopamine hydrochloride (DAꢀ HCl) in water (10 ml)
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856
Y. ITO AND S. ARIMOTO
was mixed with a hot solution containing 1.342 g
(4.98 mmol) of picric acid (pic) in MeOH (27 ml). The
mixture was filtered and the filtrate was left overnight at
room temperature. Tiny yellow crystals appeared and
these were collected by filtration and dried in vacuoꢁat
room temperature. Yield, 1.82 g (79%); m.p. 209–216 C
(decomp.) [lit.17 m.p. 189–190 ꢁC (decomp.)].
(MeOH), to afford 21 mg (21%) of 3-amino-5-nitroben-
1
zoic acid (1), whose H NMR, IR and mass spectra were
the same as those of a commercial sample.
ꢀ
Short-time pyrolyses of cocrystals DA dnba,
ꢀ
ꢀ
ꢀ
ꢀ
PA dnba, DHBA dnba, BA dnba and DMDA dn-
dnba. These pyrolyses were performed at 230–300 ꢁC
(hot-plate temperature) for 0.5–2 h. The results are sum-
marized in Scheme 3. The reaction products were ana-
ꢀ
DMDA dnba. A hot solution containing 881 mg
1
(4.15 mmol) of dnba in EtOH (20 ml) was mixed with
a hot solution containing 752 mg (4.15 mmol) of homo-
veratrylamine (O,O0-dimethyldopamine, DMDA) in
MeOH (25 ml). The mixture was filtered and the filtrate
was left overnight at room temperature. Yellow plates
appeared and these were collected by filtration and dried
in vacuo at room temperature. Yield, 1.42 g (87%); m.p.
195–199 ꢁC.
lyzed by H NMR and HPLC. Amides 5, 7 and 3b and
dihydroisoquinoline 4b were detected from the pyrolysis
mixture of the corresponding cocrystals, while the reduc-
tion product 1 was detected in all cases. Insoluble black
pigments were formed from DAꢀ dnba and DHBAꢀ dnba
and partly from DMDAꢀ dnba. The conversions were
high for DAꢀ dnba and DHBAꢀ dnba. For PAꢀ dnba,
BAꢀ dnba and DMDAꢀ dnba, the conversions were<50%.
Other cocrystals were similarly prepared.
Short-time pyrolyses of amides. The pyrolyses of
the amides 3a, 5, 6 and 7 were carried out under
conditions similar to those for the short-time pyrolyses
of cocrystals described above. The results are summar-
ized in Scheme 4. Amides containing a catechol moiety,
3a and 6, decomposed to give insoluble black pigments,
whereas amides bearing no catechol moiety, 5 and 7, gave
with negligible reactions.
Pyrolysis
ꢀ
Pyrolysis of DA dnba. A typical procedure is described
in the text. When necessary, the yield of 1 was estimated
1
from H NMR analysis (in DMSO-d6) of the pyrolysis
mixture by adding nitromethane as the integration standard.
ꢀ
Pyrolysis of DA pic. Cocrystals of DAꢀpic (218 mg)
were heated on a hot-plate (250 ꢁC) for 5 h. During this
pyrolysis, the sample turned into a black solid and a
substanial amount of an orange–yellow solid (ca 10 mg)
was sublimed. The black reaction mixture was washed
with hot MeOH several times to give a black residue
(145 mg, 72 wt%, m.p. > 300 ꢁC), with elemental analy-
sis H, 2.13; C, 53.13; N, 15.62; (O, 29.12)%. From the 1H
NMR analysis (in DMSO-d6), the orange–yellow sub-
limate was found to consist mainly of picramic acid (2)
(8% yield), which was identified by direct comparison
with a commercial sample.
Preparation of amides and dihydroisoquinolines
Preparation of 3b, 5 and 7. All the amides produced
upon pyrolysis above were prepared by alternative meth-
ods under solvent-free conditions.19 Thus, in order to
obtain 3b, 5 and 7, the corresponding amine (5 mmol) and
3,5-dinitrobenzoyl chloride (2.5 mmol) were mixed in a
porcelain mill with a pestle for 30 min. The reaction
mixture was separated by column chromatography and/or
by recrystallization with a suitable solvent, affording the
amide of interest.
3b:20 isolated by column chromatography (silica gel,
9 : 1 CHCl3–acetone) followed by recrystallization with
ꢀ
Pyrolysis of an equimolar mixture of DA HCl,
1
CHCl3, yield 92%, m.p. 195–196 ꢁC; H NMR (DMSO-
NaOH and dnba. DAꢀ HCl (103 mg, 0.53 mmol),
NaOH (21 mg, 0.53mmol) and dnba (115 mg, 0.53 mmol)
were mixed in an agate mortar with a pestle for 10 min.
The thermochemical behavior of this mixture was exam-
ined by DSC [Fig. ꢁ1(d)]. Then, pyrolysis was carried out
on a hot-plate (230 C) for 1 h. This pyrolysis mixture was
washed with MeOH several times to give a black residue
[58mg (29%), m.p. > 300 ꢁC], which was subjected to
measurements of IR, 1H NMR and UV/Vis spectra and to
elemental analysis. The IR, 1H NMR, and UV/Vis spectra
were similar to those of the black sample obtained from
pyrolysis of DAꢀ dnba. The MeOH washing was subjected
to preparative TLC on silica gel (1: 1 MeOH–benzene),
followed by preparative HPLC on Asahipak GS-320
d6), ꢂ 9.23 (1 H, t, J ¼ 7 Hz, NH), 9.02 (2 H, s, aromatic
for the dnba moiety), 8.93 (1 H, s, aromatic for the dnba
moiety), 6.85 (1 H, d, J ¼ 8.5 Hz, aromatic), 6,84 (1 H, s,
aromatic), 6.75 (1 H, d, J ¼ 8.5 Hz, aromatic), 3.73 (3 H,
s, CH3O), 3.70 (3 H, s, CH3O), 3.54 (2 H, q, J ¼ 7 Hz,
CH2NH), 2.82 (2 H, t, J ¼ 7 Hz, CH2); IR (KBr), 1669
(C O), 1542 (NO ) cmꢄ1; MS (FAB, NBA) m/z (re-
—
—
2
lative intensity, %) 376 [100, (Mþ H)þ], 375 (72, Mþ);
HRMS, calculated for C17H17N3O7 375.1067, found
375.1064. 5: recrystallized with CHCl3–acetone, yield
21
ꢁ
47%, m.p. 139–140 ꢁC (lit. m.p. 150 C). 7: recrystal-
lized with benzene, yield 57%, m.p. 202–203 ꢁC (lit.21
m.p. 201 ꢁC).
Copyright # 2003 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 849–857

EXOTHERMIC REACTION OF DOPAMINE WITH 3,5-DINITROBENZOIC ACID
857
Preparation of 3a. Immediately after quick mixing of
DAꢀ HCl, 504 mg (2.61 mmol), with NaOH, 103 mg
(2.61 mmol), in a porcelain mill, 301 mg (1.31 mmol) of
3,5-dinitrobenzoyl chloride were added. This mixture
was further ground with a pestle for 30 min. The resultant
mixture was dissolved in acetone (40 ml) and the inso-
luble residue was removed by filtration. To the filtrate was
added benzene on a water-bath, until a milky precipitate
appeared. After standing for 4 days at room temperature,
N-[2-(3,4-dihydroxyphenyl)ethyl]-3,5-dinitrobenzamide
(3a) was obtained as yellow crystals: yield 197 mg (43%),
m.p. 256–260 ꢁC (decomp.); 1H NMR (DMSO-d6), ꢂ 9.23
(1 H, t, J ¼ 7 Hz, NH), 9.11 (2 H, s, aromatic for the dnba
moiety), 8.93 (1 H, s, aromatic for the dnba moiety), 8.75
(1 H, s, OH), 8.63 (1 H, s, OH), 6.63 (1 H, d, J ¼ 8.5 Hz,
aromatic), 6.59 (1 H, s, aromatic), 6.47 (1 H, d,
J ¼ 8.5 Hz, aromatic), 3.47 (2 H, q, J ¼ 7 Hz, CH2NH),
2.70 (2 H, t, J ¼ 7 Hz, CH2); IR (KBr), 3277, 3191, 1648
(1 H, s, aromatic), 6,63 (1 H, s, aromatic), 3.98 (3 H, s,
CH3O), 3.90 (2 H, t, J ¼ 7.5 Hz, CH2N), 3.75 (3 H, s,
CH3O), 2.77 (2 H, t, J ¼ 7.5 Hz, CH2). Preparation of 6,7-
dihydroxy-1-(3,5-dinitrophenyl)-3,4-dihydroisoquinoline
(4a) was unsuccessful.
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—
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—
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¨
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Preparation of 4b. 6,7-Dimethoxy-1-(3,5-dinitrophe-
nyl)-3,4-dihydroisoquinoline (4b) was prepared from
dehydrative cyclization of amide 3b in refluxing benzene
in the presence of POCl3 (Bischler–Napieralski reac-
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Copyright # 2003 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 849–857