Synthesis and characterization of a series of 1,x-bis-(4-oxo-3,4-dihydro-1, 2,3-benzotriazin-3-yl)alkanes

Article abstract of DOI:10.1002/jhet.5570430330

Reaction of isatoic anhydride with an alkanediamine in DMF solution under mild conditions affords excellent yields of the 1,x-bis-{(2-aminobenzoyl-)amino} alkanes (2a-k), which have been characterized by IR and NMR spectroscopy, high resolution mass spect

Full text of DOI:10.1002/jhet.5570430330

May-Jun 2006
731
Synthesis and Characterization of a Series of
1,x-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes.
Naomi Hunter and Keith Vaughan*
Department of Chemistry,
Saint Mary’s University, Halifax, Nova Scotia
Canada B3H 3C3
Received October 20, 2005
O
C
O
C
X
N
H
N
H
NH2
H2N
2
HNO2
0°C
O
N
O
N
X
N
N
N
N
1
Reaction of isatoic anhydride with an alkanediamine in DMF solution under mild conditions affords
excellent yields of the 1,x-bis-{(2-aminobenzoyl-)amino}alkanes (2a-k), which have been characterized by
IR and NMR spectroscopy, high resolution mass spectrometry and elemental analysis. Diazotization of the
bis-{(2-aminobenzoyl-)-amino}alkanes in aqueous solution gives high yields of the 1,x-bis-(4-oxo-3,4-
dihydro-1,2,3-benzotriazin-3-yl)alkanes (1a-k), whch have also been characterized by IR and NMR
spectroscopy, high resolution mass spectrometry and elemental analysis. The alkanediamines employed
are as follows: ethylene diamine, 1,3-propanediamine, 1,2-propanediamine, 2-methyl-1,2-propanediamine,
2,2-dimethyl-1,3-propanediamine, 2-hydroxy-1,3-propanediamine, 1,4-diaminobutane, 1,5-diamino-
pentane, 1,3-diaminopentane (DYTEK® EP diamine), 1,6-diaminohexane and 1,7-diaminoheptane. The
alternative method of synthesis of the bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes (1) via the
diazonium salt from methyl anthranilate was explored.
J. Heterocyclic Chem., 43, 731 (2006).
Introduction.
Scheme 1
O
O
N
This paper reports the synthesis and characterization of
a series of new bis-benzo-1,2,3-triazin-3-yl)alkanes illu-
strated by structure 1 (a-k). The prime method of
synthesis is via diazotization of the bis-anthranilamide
(2), which in turn is obtained by the reaction of isatoic
anhydride (3) with the appropriate alkanediamine. Simple
benzotriazinone derivatives of type 4 have been synthe-
sized by several methods. A convenient one-pot method
is to prepare the diazonium salt 5 from methyl anthra-
nilate, and to react the diazonium salt with an excess of
the alkyl amine (RNH2) to give the linear 1-aryl-3-methyl-
triazene (6). These triazenes undergo facile cyclization to
afford the 3-alkyl-4-oxo-3,4-dihydro-1,2,3-benzotriazine
(4) [1]. An alternative general method is to react isatoic
anhydride (3) with the alkyl amine to give the anthranil-
amide (7) [2]; diazotization of the anthranilamides affords
the benzotriazinone 4.
X
N
N
N
N
N
1 a) X =CH2CH2
b) X = CH2CH2CH2
c) X = (CH2)4
d) X = (CH2)5
e) X = (CH2)6
f) X = (CH2)7
g) X = CH2CH(CH3)
h) X = CH2C(CH3)2
i) X = CH2C(CH3)2CH2
j) X = CH2CH2CH(CH2CH3)
k) X = CH2CH(OH)CH2
O
O
C
O
C
X
O
N
N
H
H
N
H
O
NH2
H2N
2
3
The use of isatoic anhydride (3) in o-aminobenzoylation
reactions has been studied for many years. The first
attempt at reaction of 3 with ammonia was reported by
Kolbe [3], who expected to produce the ammonium salt of
anthranilic acid; instead, the actual product was deter-
mined to be anthranilamide (7, R = H). Subsequently,
Staiger et al [4] investigated the reaction of 3 with a wide

732
N. Hunter and K. Vaughan
Vol 43
variety of nucleophiles and developed the synthesis of
esters, diesters, thioesters, amides and ureas. The addition
of 4-dimethylaminopyridine (DMAP) as a catalyst can
improve the efficiency of the o-aminobenzoylation [5],
which can also be affected via active esters of anthranilic
acid [6]. These reactions of isatoic anhydride are
frequently carried out under conditions of base catalysis;
in the absence of a base catalyst, the ring opening reaction
affords different products such as the isatoic esters (8)
from reaction with alcohols [7].
anhydride (i.e. 3 ꢀ 7) with ethylenediamine as the
nucleophile, in a 1:2 ratio, has also been explored.
Results and Discussion.
The initial approach to the synthesis of the bis-
benzotriazinones (1) was to adopt the method of van
Heyningen [1]. The diazonium salt (5) was reacted with
ethylene diamine to afford a moderate yield of the bis-
benzotriazinylethane (1a).
Presumably, the initially
formed bis-triazene (9) undergoes spontaneous cyclization
at both ends to afford 1a. The product of this reaction had
all of the physical characteristics of 1a described in the
literature. The melting point is within a few degrees of
the literature value, and the IR spectrum has a carbonyl
Scheme 2
CO2Me
CO2Me
RNH2
band at 1679 cm-1, which is typical for
a 3-
R
N
+
N2
N
N
H
alkylbenzotriazinone [16]. The NMR spectrum of 1a is
straightforward; the methylene protons of the two-carbon
spacer appear as a four-proton singlet at ꢁ 5.02 and the
aromatic protons appear as an 8-proton multiplet in the
range 7.60-8.40 ppm.
5
6
O
N
R
N
N
CO2H
NHCO2R
4
Attempts to reproduce the synthesis of 1a by this
method, and to extend the method to reaction with other
alkanediamines, proved to be unfruitful. Instead of a
clean solid product, we obtained oils of various textures
from gummy to clear red oil. The IR spectra of these oils
showed clearly that the major component of the oil was
methyl anthranilate, either unreacted or regenerated.
These observations are in fact consistent with the report of
van Heyningen [1], who found that reaction of 5 with
ethylene diamine gave a 60% yield of methyl anthranilate
with only 11% yield of the sought after product 1a.
Evidently, our initial success with a 42% yield of 1a was
purely serendipitous.
8
HNO2
O
O
C
O
C
-CO2
O
NHR
NHR
RNH2
O
CO2H
N
H
N
H
NH2
7
3
CO2Me
H
N
N
N
N
N
H
N
9
MeO2C
Van Heyningen explained the formation of methyl
anthranilate by suggesting that the intermediate 9
tautomerizes to the intermediate 1-alkyl-3-aryltriazene
(10) and the latter is cleaved by a nucleophile such as
water to give the anthranilate.
The products of a ring-opening reaction of isatoic
anhydride are often useful in themselves as precursors of
other heterocyclic molecules. Thus, isatoic anhydride
has been used for the synthesis of quinazolinediones [8],
benzoxazinediones [9], the benzodiazaphosphorin ring
system [10], dihydrobenzoxadiazoninediones [11],
imino-indolinones [12], the benzopyrano[3,2-c]quinoline
ring system [13] and quinolines [14]. These and other
aspects of the chemistry of isatoic anhydride have been
reviewed [15].
Scheme 3
CO2CH3
CO2CH3
N
H2O
+
N2 + ROH
9
R
NH2
methyl
N
N
H
A simple extension of the methyl anthranilate synthesis
(i.e. 5 ꢀ 6 ꢀ 4) [1] is to use ethylenediamine as the
anthranilate
10
Ha
O
primary amine.
This approach was used by van
O
N
Hb
Hc
C
R
N
H
Het
Heyningen [1] to synthesize the bis-benzotriazinone (1a),
the prototype molecule of the series described in this
paper. The objective of the present work was to build on
the previous work in order to synthesize a series of bis-
benzotriazinones with different spacer groups between the
heterocyclic rings. The alternative method to use an
extension of the anthranilamide synthesis from isatoic
Het
N
H
NH2
H
O
H
Hd
11
12
These observations suggested that the methyl
anthranilate approach is not appropriate as an entry into

May-Jun 2006
A Series of 1,x-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes
733
the series of compounds of structure 1, so we turned our
attention fully to the isatoic anhydride method.
adequate for characterization. The other members of the
series were characterized by 500MHz NMR analysis,
which provided the resolution necessary for character-
ization of these compounds. In most of the compounds of
series 2 a broad 4-proton signal at ca. 6.3 ppm originated
from the equivalent NH2 groups; only in one case, that of
2h, which was recorded in CDCl3, did the NH2 resonance
diverge from this value and was observed at 5.12 ppm.
The amide NH protons resonate at lower field, ca. 8.1-8.3
ppm, and in most cases the signal is resolved as a triplet
due to coupling with the adjacent methylene group.
These generalizations apply to the compounds of series 2
with a symmetrical carbon spacer, i.e. 2a-f, 2i and 2k.
Compound 2g is derived from 1,2-diaminopropane; the
spacer is like that in 2a, but with a methyl branch at one
Isatoic anhydride was reacted with ethylene diamine (ꢀ
equivalent) in dimethylformamide at 50 °C. Evolution of
a gas, presumably carbon dioxide, from the reaction
mixture indicated that a reaction was proceeding and the
cessation of gas evolution was taken as a sign that the
reaction was complete. Pouring the reaction mixture into
a large volume of cold water, followed by adjustment of
the pH of the mixture to 9, afforded a solid product, which
after washing and drying, was recrystallised from a
mixture of ethanol and dimethylsulfoxide to afford an
excellent yield of the 1,2-bis-{(2-aminobenzoyl)amino}-
ethane (2a). The product was identified by IR and NMR
spectroscopy and by elemental analysis. The IR spectrum
displays a carbonyl band at 1628 cm-1, a singlet amide NH
band at 3283 cm-1and the symmetric/asymmetric NH2
bands at 3369 and 3475 cm-1 The NH proton is seen at
8.29 ppm in the NMR spectrum and the NH2 protons
resonate at 6.39 ppm. The methylene protons of the
spacer group appear as a 4-proton singlet at 3.33 ppm and
the four different aromatic protons of each ring are fully
resolved in the 60 MHz spectrum.
Extension of the reaction of isatoic anhydride to those
with other alkanediamines proved to be a general method
for the synthesis of the series of 1,2-bis-{(2-amino-
benzoyl)amino}alkanes (2a-k) in high yields ranging
from 80-95% with only one exception, 2k. All products in
this series are crystalline solids with the exception of 2h,
which was repeatedly obtained as an oil. The products
were identified by IR and NMR spectroscopy in all cases,
and either by elemental analysis or by high resolution
mass spectrometry. HR-MS was preferred in those cases
where the molecular ion was observed under EI
conditions; more costly elemental analysis was employed
in the case of 2a where the molecular ion was not
observable under EI conditions. The IR spectra of the
bis-anthranilamides displayed the amide carbonyl band in
the range 1622-1687 cm-1; the NH group of the amide
side chain gives a single band in the range 3156-3303
cm-1, whereas the NH2 group gives two bands, the
symmetric and asymmetric vibrations, in the ranges 3292-
3379 and 3417-3481cm-1 In the case of the unsym-
metrically substituted 1,3-bis-{(2-aminobenzoyl)amino}-
pentane (2j), the subtly different carbonyl groups are
resolved at 1623 and 1639 cm-1, the amide NH groups are
resolved at 3232 and 3340 cm-1 and three of the four NH2
bands are resolved at 3372, 3442 and 3467 cm-1.
end.
This branching point creates considerable
asymmetry in the molecule. The amide NH protons have
different chemical shift, 7.98 and 8.27 ppm, and different
multiplicity, i.e. doublet and triplet respectively, because
of the different number of neighbouring hydrogens. The
NH2 groups are also distinct at 6.31 and 6.32 ppm, both
being 2-proton broad singlets. Similar observations are
made in the spectrum of 2j, derived from 1,3-
pentanediamine. The non-equivalent NH protons occur at
7.91 (doublet) and 8.11 (triplet) ppm and the NH2 protons
occur as broad singlets at 6.27 and 6.34 ppm.
The difference between compounds of series 2 with
symmetrical and unsymmetrical spacers is also evident in
the aromatic region of the proton spectra. The aromatic
signals of the symmetrical series is typified by compound
2c, derived from 1,4-diaminobutane. The two benzene
rings are equivalent; thus, there are four resolved
chemical shifts in the aromatic frequency range from Ha,
Hb, Hc and Hd (see structure 11). In most cases the
multiplicity is fully resolved in the 500MHz spectrum. A
signal at 7.46 ppm, assigned to Ha, is a doublet of doublets
due to vicinal coupling to Hb and long range w-coupling
to Hc. Hb is seen as a doublet of triplets at 7.11 ppm due
to vicinal coupling to Ha and Hc and long range coupling
to Hd. Similarly, Hc is a doublet of triplets at 6.49 ppm,
and Hd is a doublet of doublets at 6.67 ppm. In the
compound with an unsymmetrical spacer group, 2j, the
aromatic rings are subtly different and the 500MHZ
spectrum is almost completely resolved, showing seven
distinct aromatic chemical shifts with the multiplicity
almost completely resolved. Ha and Ha' are resolved at
7.45 and 7.51 ppm; Hb and Hb' are resolved at 7.12 and
7.13 ppm; Hc and Hc' are resolved at 6.50 and 6.52 ppm,
whereas Hd and Hd' are coincidental at 6.68 ppm.
NMR spectra of 2a-k were recorded in d6-DMSO
initially at 60MHz for convenience using the in-house
spectrometer at Saint Mary’s University. For several of
the bis-anthranilamides, namely 2a, 2b, 2h and 2i, the
resolution of the 60MHz instrument was more than
The proton signals of the spacer groups in the
symmetrical molecules of series 2 are consistent with the
structures assigned.
The straight chain spacers in
compounds 2a-f give rise to signals with appropriate

734
N. Hunter and K. Vaughan
Vol 43
chemical shifts and multiplicities; the symmetry of these
molecules is evident in the equivalence of methylene
groups. However, multiplicity is not always resolved; in
compound 2e the methylene signals at 1.34, 1.52 and
3.21ppm are all quite broad signals with hardly any fine
structure evident, whereas 2f has a very well resolved set
of signals from the seven-carbon spacer. The symmetry
of compound 2i, and the absence of vicinal coupling in
the spacer, is also reflected in the simplicity of the
spectrum. The absence of vicinal coupling in the spacer
of compound 2h is also evident in the simplicity of the
spectrum. On the other hand, the spectrum of the
seemingly symmetrical compound 2k is a little different.
The hydroxyl group proton shows up at 5.03 ppm as a
predictable doublet due to coupling with the lone tertiary
hydrogen, which itself resonates at 3.77 ppm as a sextet.
However, the two methylene groups do not appear to be
equivalent, showing up as two 2-proton quintets at 3.24
and 3.31 ppm. A possible explanation for this non-
equivalence could be the presence of a strong hydrogen
bond between NH and O (see structure 12) in solution
which would create the apparent asymmetry.
observed in expected positions.
In the symmetric
compounds, the six non-equivalent aromatic carbon atoms
are observed at ca. 114.5, 115, 116, 128, 131, and 149
ppm. In the unsymmetrical compounds, 2g and 2j, the
non-equivalent carbonyl carbon atoms are resolved, at
168.26 and 169.51 in 2g, and at 168.65 and 168.83 in 2j.
In 2g, ten of the aromatic carbons are fully resolved; only
the 149.45 carbons are not resolved. In 2j, all twelve of
the aromatic carbon atoms of the non-equivalent benzene
rings are resolved. Also in 2j, the five non-equivalent
carbon atoms of the alkane spacer are resolved.
The conversion of the bis-{(2-aminobenzoyl)-
amino}alkanes (2) to the bis-(4-oxo-3,4-dihydro-1,2,3-
benzotriazin-3-yl)alkanes (1) proceeded smoothly in
yields ranging from 35-79%. The bis-amide (2) was
diazotized with 2 equivalents of nitrous acid at low
temperature and all of the bis-benzotriazinones (1) were
obtained as stable solids, which recrystallized from
ethanol or DMSO or a mixture of the two. The IR spectra
of the bis-benzotriazinones (1) are devoid of NH bands
and display a single carbonyl band in the range 1675-1697
cm-1.
Only the butanediamine derived product (1c)
Nevertheless, the most interesting of these spacer group
NMR are those of the unsymmetrical spacers, which
contain a stereo center as in compounds 2g and 2j. In
addition to the non-equivalence of the NH, NH2 and
aromatic groups in these molecules discussed previously,
the pattern of signals from the spacer protons is complex
and informative. In 2g, the stereo centre at C2 creates a
diastereotopic methylene group at C1. The C3 methyl
group is a normal doublet at 1.15 ppm due to vicinal
coupling with the adjacent tertiary hydrogen, which itself
is a 7-line multiplet at 4.19 ppm. The diastereotopic
protons of the C1 methylene group give rise to a doublet
of triplets at 3.35 ppm. But, the most complex of all is the
proton spectrum of the 1,3-pentanediamine derivative 2j.
The methyl group at C5 of the spacer is a normal 3-proton
triplet at 0.87 ppm, but the diastereotopic methylene
group adjacent to it at 1.55 ppm is a 2-proton multiplet,
with 12 lines resolved. The diastereotopic protons of the
C2 methylene group are well resolved as two 1-proton
multiplets with 9 lines each at 1.68 and 1.77 ppm.
Similarly, the diastereotopic protons of the C1 methylene
group are well resolved as two 1-proton multiplets with 6
lines each at 3.16 and 3.34 ppm. The latter multiplet is
partially obscured by the water peak at 3.31 ppm. Lastly,
the tertiary proton at C3 is found at 3.91 ppm as a 1-
proton multiplet.
displayed two distinct carbonyl bands at 1673 and 1694
cm-1, which could be attributed to symmetric and
asymmetric vibrations. The OH group of compound 1k
1
gives rise to a broad band at 3328 cm-1 The H NMR
spectra of the bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-
3-yl)alkanes (1) clearly display two sets of signals, those
from the aromatic protons and those arising from the
protons of the alkane spacer groups. As in the case of the
bis-{(2-aminobenzoyl-)amino}alkanes, the compounds of
series 1 can be divided into a group with a symmetrical
spacer moiety and a group with an unsymmetrical spacer.
In those compounds with a symmetrical spacer group, the
four protons of each equivalent benzene ring are resolved
(at 500MHz) with multiplicity of either a doublet of
triplets or a doublet of doublets; in some cases the latter is
only resolved as a doublet.
The eight non-equivalent aromatic protons in the
500MHz spectrum of 1j, which has an unsymmetrical
spacer group, are all fully resolved with the predicted
multiplicity. The proton signals of the spacer group in 1j
are incredibly complex due to the presence of a stereo
center, but can be interpreted to a certain level. The
terminal methyl group (C5) is a triplet, as expected, at
0.81 ppm.
The diastereotopic protons of the C4
methylene group are resolved as a one hydrogen ten-line
multiplet at 1.80-1.85 ppm and a second one-hydrogen
ten-line multiplet at 1.89-1.95 ppm. The methine proton
at C3 gives rise to a septet at 4.71 ppm, and the
diastereotopic protons of the C2 methylene group give
rise to two 14-line multiplets at 2.33-2.39 and 2.48-2.53
ppm, each integrating for one hydrogen. Finally, the
Selected compounds in the series 2a-k were analyzed
by 13C NMR spectroscopy. In general the amide carbonyl
carbon is observed at ca. 169 ppm and the methylene
carbon adjacent to the amide nitrogen is observed at ca.
39 ppm. Other carbon atoms of the spacer group are

May-Jun 2006
A Series of 1,x-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes
735
Scheme 4. Compound 13 is the closest thing to an acyclic
analogue of the prototype compound 1a, so it would seem
appropriate to compare their characteristics; 13 is a
relatively low melting solid, soluble in non-polar solvents,
in contrast to 1a. The carbonyl bands are found at 1710
cm-1 in 13 and at 1679 cm-1 in 1a, which is predictable since
1a is an amide and 13 is an ester. The chemical shifts of
the protons of the two-carbon spacer are significantly
different, 5.02 ppm in 1a and 4.08 ppm in 13.
A further development of this project will be to
compare the solid state structures of the compounds of
type 1 with the structures of compounds of type 13, which
have already been studied [21]. Compounds of type 13
showed significant divergence in the preferred solid-state
conformation, either the folded gauche conformation or
the extended staggered conformation, dependent on the
nature of the substituent group in the aryl ring. It will be
of interest to see if the length of the polymethylene spacer
group in 1 influences the conformation of the molecule in
the solid state. At a certain point, it would be expected
diastereotopic protons of the methylene group at C1 are
observed as two one-proton multiplets at 3.99 and 4.08
ppm.
shows the effect of the unsymmetrical spacer group; there
are two carbonyl carbon signals at 155.3 and 155.7 ppm,
the five unique carbon atoms of the spacer group are
clearly observed and eleven of the twelve unique aromatic
carbon atoms are resolved.
The protons of the spacer groups in the compounds of
series 1 with symmetrical spacers give rise to signals in
the NMR spectra that are consistent with the structures, as
illustrated by the spectrum of 1e, derived from 1,6-
diaminohexane. The symmetry of the 6-carbon spacer is
manifested by a 4-proton quintet at 1.51 ppm (methylene
groups at C3 and C4), a 4-proton quintet at 1.95 ppm
(methylene groups at C2 and C5) and a 4-proton triplet at
4.48 ppm (methylene groups at C1 and C6). The carbon
atoms of this spacer group are seen at 26.23(C3/C4),
28.73(C2/C5) and 49.70(C1/C6). In general, the carbonyl
carbon in compounds of series 1 is found at ca. 155.5.
The aromatic carbon atoms of the symmetrical
compounds in series 1 are observed at ca. 119.8, 125.1,
128.3, 132.2, 134.5 and 144.3 ppm.
The 13C NMR spectrum of compound 1j also
that the molecule of
1 could assume a folded
conformation held in place by ꢀꢀꢀ stacking between the
phenyl rings.
Conclusion.
Finally it should be noted that Stevens et al synthesized
a
series of bis(imidazotetrazinones) (14) [22] by
The results reported in this paper clearly show that the
bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes
(1) can be synthesized and characterized. These
compounds are stable, crystalline solids. This study
complements the on-going work in this laboratory, which
is primarily directed at the synthesis of bis-triazenes [17].
The “triazene”, e.g. 10, is the non-cyclic, or open-chain,
equivalent of the heterocyclic “triazine”. Among the
several types of bis-triazene that we have synthesized
recently [18,19], one group stands out as being relevant to
the bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes
(1) reported here. That group is the series of 1,2-bis-(1-
aryl-3-methyltriazen-3-yl)ethanes (Ar-N=N-NMe-CH2CH2
-NMe-N=N-Ar) previously reported [20]; of particular
relevance is the compound of that series derived from
methyl anthranilate, which is the bis-triazene (13) shown in
interaction of 5-diazoimidazole-4-carboxamide and a
series of diisocyanates. These bis(imidazotetrazinones)
are related in structure to the antitumour agent temozol-
omide [23], but the presence of the polymethylene spacer
does not substantially affect the antitumour activity
relative to the unlinked imidazotetrazine.
EXPERIMENTAL
All reagents were reagent grade materials purchased from
Sigma-Aldrich Canada Ltd and were used without further
purification. Melting points were determined on a Fisher-Johns
melting point apparatus and are uncorrected. Infrared spectra
were obtained using Nujol mulls with a Bruker Vector 22
spectrometer. 1H and 13C NMR spectra were obtained with
either (i) the Bruker 500MHz spectrometer at the Atlantic
Regional Magnetic Resonance Center at Dalhousie University,
or (ii) the ANASAZI 60MHz EFT spectrometer at SMU.
Chemical shifts were recorded in solution in CDCl3 or d6-DMSO
(as specified) at 20 °C, and are relative to TMS as internal
standard. The peak multiplicities are abbreviated as follows:
s(singlet), d(doublet), t(triplet, q(quartet), dd(doublet of
doublets), dt(doublet of triplets), dq(doublet of quartets),
m(multiplet), br(broad). Elemental Analyses were performed by
the Canadian Microanalytical Service Ltd., Delta, B.C. High
resolution mass spectral data (EI) were obtained with the CEC
21-110B mass spectrometer at Dalhousie University in Halifax.
The standard deviation of mass measurement is +/- 0.0008amu,
which is an average of 3.6 ppm over the mass range 100 to 300
amu.
Scheme 4
CO2Me
Me
N
N
N
N
N
N
Me
MeO2C
13
H2NOC
N
CONH2
N
N
N
N
O
N
N
N
N
N
X
O
14

736
N. Hunter and K. Vaughan
Vol 43
Synthesis of the 1,x-bis-{(2-aminobenzoyl-)amino}alkanes (2a-
k).
1,6-Bis-{(2-aminobenzoyl-)amino}hexane (2e).
2e: 84%, pale yellow prisms, m.p. 176-177°C (ethanol), IR
1
General Procedure.
ꢀ
: 1642, 3288, 3365, 3481 cm-1; H nmr (500MHz, DMSO-
max
d6): ꢁ 1.34(4H, br), 1.52(4H,br), 3.21(4H, br), 6.34(4H, br, NH2),
6.51(2H, m), 6.68(2H, m), 7.13(2H,m), 7.46(2H,br), 8.16(2H,
br, NH)ppm; 13C nmr (125.77Hz, DMSO-d6): ꢁ 26.8, 29.6, 39.2,
115.0, 115.6, 116.7, 128.5, 131.9, 150.0, 169.7 ppm; HR-MS
m/z calc’d for C20H26N4O2: 354.2055; found: 354.2058 (EI).
Isatoic anhydride (8.20 g, 0.05 mol) was dissolved in
dimethylformamide (“DMF”) (25.0 mL) and the solution was
warmed to 50°C in a water bath. The appropriate alkane-
diamine (0.025 mol) was dissolved in DMF (10.0 mL) and this
solution was added slowly to the warm isatoic anhydride
solution over a period of one hour. The reaction was then
allowed to run for approximately 3.5 h until carbon dioxide
evolution had ceased. The reaction mixture was then poured
into cold water (400.0 mL) creating a slurry, which was
basified to pH 9 with concentrated potassium hydroxide
solution. The product was then filtered by suction filtration,
washed with water, until the wash was caustic free, and dried
under suction. Complete drying was achieved in a vacuum
dessicator overnight and the product was recrystallized from
ethanol or dimethylsulfoxide (“DMSO”) to afford the bis-
anthranilamides (2) as follows:
1,7-Bis-{(2-aminobenzoyl-)amino}heptane (2f).
2f: 95%, white needles, m.p. 140-143°C (ethanol), IR ꢀ
:
max
1624, 3303, 3379, 3470 cm-1; H nmr (500MHz, DMSO-d6): ꢁ
1.32(6H, m), 1.52 (4H, quintet, J = 6.8Hz), 3.20(4H, quartet, J =
6.6Hz), 6.34(4H, br s, NH2), 6.50(2H, dt, J = 1.2 & 8.0Hz),
6.68(2H, dd, 1.1 & 8.3Hz), 7.12(2H, dt, J = 1.3 & 7.6Hz),
7.45(2H, dd, J = 1.2 & 7.9Hz), 8.16(2H, t, J = 5.5Hz, NH)ppm;
13C nmr (125.77Hz, DMSO-d6): ꢁ 27.0, 29.1, 29.6, 39.2, 115.0,
115.6, 116.7, 128.5, 131.9, 150.0, 169.2ppm; HR-MS m/z calc’d
for C21H28N4O2: 368.2212; found: 368.2210 (EI).
1
1,2-Bis-{(2-aminobenzoyl-)amino}propane (2g).
1,2-Bis-{(2-aminobenzoyl-)amino}ethane (2a).
2g: 83%, white needles, m.p. 178-180°C (ethanol), IR ꢀ
:
2a: 81%, lustrous cream needles, m.p. 246-247°C (ethanol/
: 1628, 3283, 3369, 3475 cm-1; 1H nmr
max
1627, 3283, 3363, 3469 cm-1; H nmr (500MHz, DMSO-d6): ꢁ
1.15(3H, d, J = 6.7Hz), 3.35(2H, dt, J = 1.6 & 6.3Hz), 4.19(1H,
septet, J = 6.8Hz), 6.31(2H, s, NH2), 6.32(2H, s, NH2), 6.50(2H,
dq, J = 1.1 & 6.7Hz), 6.67(1H, dd, J = 1.0 & 2.6Hz), 6.68(1H,
dd, J = 0.9 & 2.6Hz), 7.12(2H, dt, J = 1.4 & 7.7Hz), 7.45(1H,
dd, J = 1.2 & 8.0Hz), 7.48(1H, dd, J = 1.2 & 7.8Hz), 7.98(1H, d,
J = 7.9Hz), 8.27(1H, t, J = 5.8Hz)ppm; 13C nmr (125.77Hz,
DMSO-d6): ꢁ 18.0, 30.6, 43.9, 44.9, 114.5, 114.6, 114.9, 115.1,
116.2, 116.2, 128.0, 128.2, 131.5, 131.6, 149.5, 168.5 and
169.3ppm; HR-MS m/z calc’d for C17H20N4O2: 312.1586; found:
312.1590 (EI).
1
DMSO), IR ꢀ
max
(60MHz, DMSO-d6): ꢁ 3.33(s, 4H), 6.39(4H, br, NH2), 6.50(2H,
m), 6.68(2H, dd, J = 1.3 & 8.2Hz), 7.08(2H, dt, J = 1.4 &
6.7Hz), 7.48 (2H, dd, J = 1.3 & 7.7Hz), 8.29(2H, br, NH)ppm ;
Anal. calc’d for C16H18N4O2: C 64.43, H 6.04, N 18.79; found: C
64.96, H 6.33, N 18.53%.
1,3-Bis-{(2-aminobenzoyl-)amino}propane (2b).
2b: 88%, light beige prisms, m.p.170-172°C(ethanol), IR
:1622, 3205, 3292, 3417 cm-1; 1H nmr (60MHz, DMSO-d6):
ꢀ
max
ꢁ 1.76(2H, quintet, J = 6.8Hz), 3.26(4H, t, J = 6.6Hz), 6.39(4H,
br, NH2), 6.52(2H, br), 6.71(2H, dd, J = 1.4 & 7.8Hz), 7.11(2H,
dt, J = 1.4 & 6.8Hz), 7.50(2H, dd, J = 1.4 & 7.9Hz) and
8.23(2H, t, J = 6.0Hz, NH)ppm;
2-Methyl-1,2-bis-{(2-aminobenzoyl-)amino}propane (2h).
1
2h: 95%, oil, IR ꢀ
: 1687, 3156, 3326, 3468 cm-1; H nmr
max
(60MHz, CDCl3): ꢁ 1.50(6H, s), 3.30(2H, br), 5.12(4H, br,
NH2), 6.55-7.81 (8H, m), and 8.3(2H, br, NH)ppm; HR-MS m/z
calc’d for C18H22N4O2: 326.1742; found: 326.1754 (EI).
HR-MS m/z calc’d for C17H20N4O2: 312.1586 ; found:
312.1587 (EI).
1,4-Bis-{(2-aminobenzoyl-)amino}butane (2c).
2,2-Dimethyl-1,3-bis-{(2-aminobenzoyl-)amino}propane (2i).
2c: 84%, beige needles, m.p.199-200°C(ethanol/DMSO), IR
1
max
ꢀ
: 1628, 3298, 3356, 3471 cm-1; H nmr (500MHz, CDCl3):
89%, white prisms, m.p. 204-206°C (ethanol), IR ꢀ
: 1646,
max
3159(w), 3339, 3477 cm-1; 1H nmr (60MHz, DMSO-d6): ꢁ
0.91(6H, s), 3.38(4H, s), 6.33(4H, br, NH2), 6.49(2H, br d, J =
8.2Hz), 6.72(2H, br d, J = 7.1Hz), 7.12(2H, br d, J = 6.8Hz),
7.54(2H, br d, J = 7.8Hz), 8.32(2H, t, J = 5.9Hz, NH)ppm; HR-
MS m/z calc’d for C19H24N4O2: 340.1899; found: 340.1893 (EI).
ꢁ 1.54(4H, br t), 3.23(4H, br m, J = 5.7), 6.35(4H, br s, NH2),
6.49 (2H, dt, J = 1.0 and 7.5Hz), 6.67(2H, dd, J = 0.9 & 7.8Hz),
7.11(2H, dt, J = 1.3 & 7.6Hz), 7.46(2H, dd, J = 1.2 & 7.8Hz),
8.18(2H, t, J = 5.5Hz)ppm.
13C nmr (125.77Hz, CDCl3): ꢁ 26.7, 38.5, 114.5, 115.0, 116.2,
128.0, 131.4, 149.5, 168.8ppm; HR-MS m/z calc’d for
C18H22N4O2: 326.1742; found: 326.1744 (EI).
1,3-Bis-{(2-aminobenzoyl-)amino}pentane (2j).
2j: 84%, tiny white needles, m.p. 145-146°C(ethanol), IR
1
max
1,5-Bis-{(2-aminobenzoyl-)amino}pentane (2d).
ꢀ
: 1623, 1639, 3232, 3340, 3372, 3442, 3467 cm-1; H nmr
2d: 80%, pale yellow rosettes, m.p. 141-142°C (ethanol), IR
1
max
(500MHz, CDCl3): ꢁ 0.87(3H, t, J = 7.4Hz), 1.55(2H, m – 12
lines resolved), 1.68(1H, m – 9lines), 1.77(1H, m – 9 lines),
3.16(1H, sextet, J = 6.7Hz), 3.34(1H, m), 3.91(1H, m, 9 lines, J
= 4.25Hz), 6.27(2H, br, NH2), 6.34(2H, br, NH2), 6.50(1H, dt, J
= 0.9 & 7.9Hz), 6.52(1H, dt, J = 0.9 & 8.0Hz), 6.68(2H, dt, J =
0.9 & 7.3Hz), 7.12(1H, dt, J = 1.5 & 7.1Hz), 7.13(1H, dt, J = 1.5
& 7.2Hz), 7.45(1H, dd, J = 1.2 & 8.0Hz), 7.51(1H, dd, J = 1.3 &
ꢀ
: 1628, 3298, 3370, 3471 cm-1; H nmr (500MHz, CDCl3):
ꢁ 1.34(2H, quintet, J = 7.5Hz), 1.53(4H, quintet, J = 7.3Hz),
3.21(4H, q, J = 6.6Hz), 6.34(4H, br s, NH2 ), 6.49(2H, dt, J = 0.9
& 7.5Hz), 6.67(2H, dd, J = 0.9 & 7.8Hz), 7.11(2H, dt, J = 1.5 &
7.7Hz), 7.45(2H, dd, J = 1.2 & 7.9Hz), 8.15(2H, t, J =
5.4Hzppm);13C nmr (125.77Hz, CDCl3): ꢁ 24.0, 28.8, 38.7,
114.5, 115.1, 116.2, 128.0, 131.4, 149.4, 168.7ppm; HR-MS m/z
calc’d for C19H24N4O2: 340.1899; found: 340.1906 (EI).
7.9Hz), 7.91(1H, d, J = 8.7), and 8.11(1H, t, J = 5.4Hz)ppm; 13
nmr (125.77Hz, CDCl3): ꢁ 10.6, 27.1, 34.1, 36.5, 48.1, 114.5,
C

May-Jun 2006
A Series of 1,x-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)alkanes
737
114.5, 115.0, 115.5, 116.1, 116.2, 127.9, 128.1, 131.4, 131.4,
149.3, 149.5, 168.7, and 168.8 ppm. HR-MS m/z calc’d for
C19H24N4O2: 340.1899; found: 340.1893 (EI).
Anal. Calcd. for C19H18N6O2: C 62.97, H 5.01, N 23.19:
Found: C 62.99, H 5.01, N 23.25
1,6-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)hexane (1e).
2-hydroxy-1,3-bis-{(2-aminobenzoyl-)amino}propane (2k).
2k: 38%, small white prisms, m.p. 183-185°C (ethanol), IR
1e: 66%, white needles, m.p. 186-187°C (DMSO), IR ꢀ
:
max
1681 cm-1; H nmr (500MHz, CDCl3): ꢁ 1.51(4H, quintet, J =
5.5Hz), 1.95(4H, quintet, J = 7.5Hz), 4.48(4H, t, J = 7.5Hz),
7.79(2H, dt, J = 1.0 & 8.1Hz ), 7.94(2H, dt, J = 1.4 & 8.4Hz),
8.14(2H, d, J= 8.1Hz ), 8.34(2H, d, J = 0.9 & 8.0Hz) ppm; 13C
nmr (125.77Hz, CDCl3): ꢁ 26.2, 28.7, 49.7, 119.8, 125.1, 128.2,
132.2, 134.7, 144.3, 155.5 ppm;:HR-MS m/z calc’d for
C20H20N6O2: 376.1647; found: 376.1632 (EI).
1
ꢀ
: 1625, 3195 (OH, br), 3287, 3344, 3459 cm-1; 1H nmr
max
(500MHz, CDCl3): ꢁ 3.24(2H, quintet, J = 6.4Hz), 3.31(2H,
quintet, J = 6.2Hz), 3.77(1H, sextet, J = 4.6Hz), 5.03(1H, d, J =
5.0Hz, OH), 6.35(4H, br, NH2), 6.51(2H, dt, J = 0.9 & 7.5Hz),
6.69(2H, dd, J = 0.9 & 7.8Hz), 7.13(2H, dt, 1.4 & 7.7Hz),
7.50(2H, dd, J = 1.0 & 8.0Hz) and 8.15(2H, t, J = 5.8Hz, NH)
ppm; 13C nmr (125.77Hz, CDCl3): ꢁ 43.2, 68.6, 114.6, 114.8,
116.3, 128.0, 131.6, 149.5 and 169.1 ppm; HR-MS m/z calc’d
for C17H20N4O3: 328.1535; found: 328.1548 (EI).
1,7-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)heptane
(1f).
1f: 64%, white needles, m.p. 144-146°C (ethanol), IR ꢀ
:
max
Synthesis of the 1,x-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-
3-yl)alkanes (1 a-k).
1697 cm-1; H nmr (500MHz, CDCl3): ꢁ 1.45(6H, m), 1.93(4H,
quintet, J = 7.5Hz), 4.47(4H, t, J = 7.5Hz), 7.79(2H,dt, J = 1.1 &
7.7Hz), 7.94(2H, dt, J = 1.3 & 7.8Hz), 8.14(2H, d, J = 8.1Hz),
8.35(2H, dd, J = 0.9 & 7.9Hz) ppm; 13C nmr (125.77Hz,
CDCl3): ꢁ 26.5, 28.7, 28.8, 49.8, 119.8, 125.1, 128.2, 132.2,
134.6, 144.3 and 155.5 ppm; HR-MS m/z calc’d for C21H22N6O2:
390.1804; found: 390.1805 (EI).
1
General Procedure.
The bis-anthranilamide (2) (0.01 mol) was dissolved in 3 M
hydrochloric acid (25.0 mL) and cooled in an ice/salt bath to 0
°C. The solution was diazotized with sodium nitrite (1.72 g) in
water (6.0 mL) keeping the temperature around 0 °C. The
mixture was stirred in the cold for 2.0 h. At this point, any
insoluble material was removed by cold vacuum filtration, and
the filtrate was then treated with saturated sodium bicarbonate
solution to precipitate the product, which was separated by
vacuum filtration, dried and recrystallised from ethanol or
DMSO to afford the bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-
3-yl)alkanes (1a-k) as follows:
1,2-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)propane
(1g).
1g: 61 %, white needles, m.p. 133-134°C (ethanol), IR ꢀ
:
max
1679.5 cm-1;
1H nmr (60MHz, CDCl3): ꢁ 1.81(3H, d, J = 7.0Hz), 5.01(2H,
d, J = 6.2Hz), 5.82(1H, m, J = 6.4Hz), 7.29-8.27(8H, m) ppm;
HR-MS m/z calc’d for C17H14N6O2: 334.1178; found: 334.1181
(EI).
1,2-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)ethane (1a).
1a: 70%, pale yellow needles, m.p. 217-219 °C (DMSO) {lit.
2-Methyl-1,2-bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)-
propane (1h).
m.p. [1] 213-215°C}, IR ꢀ
CDCl3): ꢁ 5.02(4H, s), 7.60-8.40(8H, m) ppm; HR-MS m/z
: 1679 cm-1; 1H nmr (60MHz,
max
1h: 79%, white needles, m.p. 159-160°C (ethanol), IR ꢀ
:
max
calc’d for C16H12N6O2: 320.1021; found: 320.1023 (EI).
1681.5 cm-1;
1H nmr (60MHz, CDCl3): ꢁ 1.95(6H, s), 5.32(2H, s), 7.68-
8.40(8H, m) ppm.
1,3-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)propane (1b).
1b: 35%, fine white needles, m.p. 188-189 °C (ethanol), IR
Anal. Calcd. for C18H16N6O2: C 62.07, H 4.60, N 24.14.
Found: C 62.34, H 4.71, N 24.46%.
ꢀ
: 1683 cm-1; 1H nmr (60MHz, CDCl3): ꢁ 2.56(2H, quintet, J
max
= 6.9Hz), 4.65(4H, t, J = 7.2Hz), 7.28-8.30(8H, m)ppm.
Anal. Calcd. for C17H14N6O2: C 61.08, H 4.19, N 25.15.
Found: C 60.80, H 4.16, N 25.36 %.
2,2-Dimethyl-1,3-bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-
yl)propane (1i).
1i: 66%, fine white powder, m.p. 180-182°C (ethanol), IR
: 1687 cm-1; 1H nmr (60MHz, CDCl3): ꢁ 1.16(6H, s),
4.62(4H,s), 7.76-8.40(8H, m) ppm; HR-MS m/z calc’d for
1,4-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)butane (1c).
1c: 48%, feathery white needles, m.p. 225-228°C (DMSO),
ꢀ
max
IR ꢀ
: 1694, 1673 cm-1; 1H nmr (500MHz, CDCl3): ꢁ
C19H18N6O2: 362.1491; found: 362.1495 (EI).
max
1.86(4H, m), 4.11(4H, br t, J = 5.9Hz), 7.01(2H, dt, J = 0.8 &
6.8Hz), 7.14(2H, dt, J = 1.2 & 6.8Hz), 7.32(2H, d, J = 7.3Hz),
and 7.50(2H, dd, J = 0.7 & 7.2Hz)ppm; 13C nmr (125.77Hz,
CDCl3): ꢁ 26.1, 49.2, 119.8, 125.1, 128.3, 132.4, 134.8, 144.3
and 155.5 ppm.
1,3-bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)pentane (1j).
1j: 55%, thick white needles, m.p. 101-103°C (ethanol), IR
ꢀ
: 1687.5 cm-1;
max
1H nmr (500MHz, CDCl3): ꢁ 0.81(3H, t, J = 7.5Hz), 1.80-
Anal. Calcd. for C18H16N6O2: H 4.60, N 24.14. Found: H 4.31,
N 23.91 %.
1.85(1H, m – 10lines), 1.89-1.95(1H, m – 10 lines resolved),
2.33-2.39(1H, m – 14 lines resolved), 2.48-2.53(1H, m – 14
lines resolved), 3.99(1H, m – 7 lines), 4.08(1H, quintet, J =
6.3Hz), 4.71(1H, septet, J = 4.2Hz), 6.99(1H, dt, J = 0.9 &
8.1Hz), 7.01(1H, dt, J = 0.9 & 8.1Hz), 7.11(1H, dt, J = 1.5 &
7.5Hz), 7.13(1H, dt, J = 1.5 & 7.5Hz), 7.27(1H, d, J = 7.5Hz),
7.30(1H, d, J = 7.5Hz), 7.43(1H, dd, J = 1.5& 7.4Hz), and
7.49(1H, dd, J = 1.5 & 7.4Hz) ppm;
1,5-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)pentane (1d).
1d: 73%, white needles, m.p. 193-195°C (ethanol/DMSO),
IR ꢀ
: 1675 cm-1;
max
1H nmr (60MHz, CDCl3): ꢁ 1.71(2H, m), 2.05(4H, m),
4.50(4H, t, J = 6.0Hz), 7.71-8.40(8H, m) ppm.

738
N. Hunter and K. Vaughan
Vol 43
13C nmr (125.77Hz, CDCl3): ꢀ 28.2, 40.8, 44.4, 54.9, 62.2,
129.0, 129.2, 133.1, 133.3, 135.4, 135.5, 138.4, 140.2, 140.2,
146.8, 147.1, 155.3 and 155.7 ppm.
Anal. Calcd. for C19H18N6O2: H 5.01, N 23.19. Found: H 4.94,
N 22.78%.
Atlantic Region Magnetic Resonance Centre at Dalhousie
University for providing NMR spectra, and to the Maritime
Mass Spectrometry Laboratory at Dalhousie University for
providing high resolution Mass spectra, with particular thanks to
Mr. Xiao Feng for his assistance.
2-Hydroxy-1,3-bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)-
propane (1k).
REFERENCES
48%, fine burgundy powder, m.p. 213-217°C (ethanol), IR
: 1681, 3328(br) cm-1;
*
Corresponding author (keith.vaughan@smu.ca).
ꢁ
[1] E. M. van Heyningen, J. Am. Chem. Soc., 77, 6562 (1975).
[2] R. H. Clark and E. C. Wagner, J. Org. Chem., 9, 55 (1944).
[3] H. Kolbe, J. Prakt. Chem. [2], 30, 467 (1884).
[4] R. P. Staiger and E. B. Miller, J. Org. Chem., 24, 1214
(1959); R. P Staiger and E. C. Wagner. J. Org. Chem., 18, 1427 (1953).
[5] M. C. Venuti, Synthesis, 266 (1982).
max
1H nmr (500MHz, CDCl3): ꢀ 3.72(1H, d, J = 5.1Hz, OH),
4.71-4.79(5H, m), 7.83(2H, dt, J = 0.9 & 7.5Hz), 7.97(2H, dt, J
= 1.4 & 7.7Hz), 8.18(2H, d, J = 8.1Hz) and 8.36(2H, dd, J = 0.9
& 8.0Hz)ppm; 13C nmr (125.77Hz, CDCl3): ꢀ 53.7, 69.6, 119.6,
125.2, 128.5, 132.7, 135.2, 144.12 and 156.6 ppm.
[6] C. Hinman and K. Vaughan, Synthesis, 719 (1980).
[7] D. A. Heyman, J. Heterocyclic Chem., 15, 1131 (1978).
[8] R.L. Jacobs, J. Het. Chem. 7, 1337 (1970)
[9] G. E. Hardtmann, G. Koletar and O. R. Pfister, J.
Heterocyclic Chem., 12, 565 (1975).
Anal. Calcd. for C17H14N6O3: C 58.28, H 4.03, N 23.99.
Found: C 58.51, H 4.07, N 24.05%.
1,2-Bis-(4-Oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)ethane (1a).
Alternate Method.
[10] G. M. Coppola and R. I. Mansukhani, J. Heterocyclic Chem.,
15, 1169 (1978).
Methyl anthranilate (1.51 g, 0.01 mol) was dissolved in 3 M
hydrochloric acid (12.0 mL) and cooled to between 0-5 °C. The
cold solution was diazotized with a solution of sodium nitrite
(0.75 g) in water (3.0 mL) and then stirred for 0.5 h. in the cold.
Ethylenediamine (0.307 g, 0.005 mol) dissolved in water (2.0 mL)
was added slowly to the cold diazonium salt solution with stirring
and cooling. The mixture was then neutralized with saturated
sodium bicarbonate solution (15.5 mL), whereupon a precipitate
was formed. The solid was isolated by suction filtration, dried
overnight and then recrystallised from ethanol to afford the pure
[11] S. Barcza, G. M. Coppola and M. J. Shapiro, J. Heterocyclic
Chem., 16, 439 (1979).
[12] G. M. Coppola, J. Heterocyclic Chem., 16, 827 (1979).
[13] G. M. Coppola and G. E. Hardtmann, J. Heterocyclic Chem.,
16, 829 (1979).
[14] G. M. Coppola and G. E. Hardtmann, J. Heterocyclic Chem.,
16, 1605 (1979).
[15] G. M. Coppola, Synthesis, 505 (1980).
[16] R. J. LeBlanc and K. Vaughan, Can. J. Chem., 50, 2544
(1972)
[17] K. Vaughan, Org. Prep. Proc. Int., 33, 59 (2001).
[18] V. R. Little, R. Tingley and K. Vaughan, Can. J. Chem., 83,
471 (2005).
[19] S. L. Moser and K. Vaughan, Can. J. Chem., 82, 1725
(2004).
1,2-bis-(4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yl)ethane
42.5% yield, m.p. 218-220 °C {lit. m.p. [1] 213-215 °C};
(1a),
IR ꢁ
: 1679cm-1; 1H nmr (60MHz, CDCl3): ꢀ 5.02(4H, s),
max
7.62-8.40(8H, m). This product was identical in all respects (IR,
NMR, m.p.) with the product of diazotization of 1,2-bis-{(2-
aminobenzoyl-)amino}ethane (2a) described above.
[20] D. L. Hooper, I. R. Pottie, M. Vacheresse and K. Vaughan,
Can. J. Chem., 76, 125 (1998).
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The authors are grateful to the Natural Sciences and
Engineering Council of Canada (NSERC) for a Discovery Grant
to the principal author (KV) and an Undergraduate Summer
Research Award (2004) to Naomi Hunter. Financial support
was also provided by the Faculty of Graduate Studies and
Research at Saint Mary’s University. We are also grateful to the