New α-amido-α-aminonitrones as building blocks for constructing heterocyclic systems

Article abstract of DOI:10.1055/s-2008-1067236

New, stable α-amido-α-aminonitrones were obtained in good yields from 3-oxobutyric acid N-pyridin-2-ylamides and nitrosobenzene. The α-amido-α-aminonitrones were then used as new, versatile building blocks to obtaining various heterocycles with both bielectrophilic and binucleophilic reagents. With diiodomethane as reagent, 1,2,5-oxadiazine derivatives were formed, whereas reactions with aromatic 1,2-, 1,3- and 1,4-diamines yielded quinoxaline, quinazoline, perimidine, and dibenzo[d,f][1,3]diazepine derivatives, respectively. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067236

PAPER
2977
New a-Amido-a-aminonitrones As Building Blocks for Constructing
Heterocyclic Systems
a
-Amido-
a
-amin
a
r
ilding
B
t
locks
f
o
or
H
eterocyc
s
lic System
z
s
Trzewik,* Dariusz Cież, Maciej Hodorowicz, Katarzyna Stadnicka
Faculty of Chemistry, Jagiellonian University, ul. Romana Ingardena 3, 30-060 Kraków, Poland
Fax +48(12)6340515; E-mail: trzewik@chemia.uj.edu.pl
Received 27 May 2008
MeO NHPh
Abstract: New, stable a-amido-a-aminonitrones were obtained in
Me
NHR
1: X = S, R = Ar
2: X = O, R = Ar
3: X = O, R = 2-Py
good yields from 3-oxobutyric acid N-pyridin-2-ylamides and ni-
trosobenzene. The a-amido-a-aminonitrones were then used as
new, versatile building blocks to obtaining various heterocycles
with both bielectrophilic and binucleophilic reagents. With di-
iodomethane as reagent, 1,2,5-oxadiazine derivatives were formed,
whereas reactions with aromatic 1,2-, 1,3- and 1,4-diamines yielded
quinoxaline, quinazoline, perimidine, and dibenzo[d,f][1,3]diaz-
epine derivatives, respectively.
O
X
1–3
Figure 1
blocks derived from amides of 3-oxoacids 1.4a,b,d,5 Over
the past few years, they have reported on the syntheses of
various heterocyclic rings of 1,3- and 1,4-diazines4 from
thioanilides 1, whereas anilides 2 turned out to be unreac-
tive.5 In an attempt to modify the reactivity of 1, we decid-
ed to introduce pyridin-2-yls instead of aryl substituents in
the amide moieties of 1, along with replacing the sulfur
atom with an oxygen atom, in order to obtain pyridilides
3 (Figure 1).
Key words: building blocks, nitrones, heterocycles, alkylation, cy-
clisation
Nitrones are widely used in organic synthesis,1a–c where
they mainly serve as electrophiles and 1,3-dipoles,1d–f also
in a stereospecific manner,1d–h and spin-traps;1a–c,i–k they
have also been used as active equivalents of the carbonyl
group.1c,l–m,2a However, there have only been a few reports
regarding a-aminonitrones.2 They can be derived from ni-
triles and hydroxylamines,2a from imidoformic acid esters
or a-chloroimines,2g from hydroxylamines and methylene
amines,2g,3d from secondary amines2f and nitroso com-
pounds, and from other nitrones.2b The tautomerism2a,3d
and the crystal structure2a,3d of a-aminonitrones have been
studied, but the only report on using such compounds in
synthesis was provided by Prabhakar and co-workers,2a
who exploited nucleophilic centres in a-aminonitrones in
monoalkylation and diacylation reactions. The authors re-
ported only one reaction of an a-aminonitrone as a bielec-
trophilic reagent. a-Amido-a-aminonitrones had not been
previously reported.
In the reactions of ethyl acetoacetate and variously substi-
tuted 2-aminopyridines, we obtained the corresponding
pyridilides 4a–d (4d had not previously been reported),
which were then treated with nitrosobenzene in methanol
in an attempt to obtain C-2 disubstituted products of type
3.6 Using two equivalents of nitrosobenzene yielded unex-
pected products; the spectra and elemental analyses en-
couraged the conclusion that the actual products were
nitrones 5a–e (Scheme 1).
The structure of 5a was confirmed by an X-ray crystal
structure analysis.3a The experiment showed that the com-
pound crystallised from methanol with about one mole-
cule of solvent per two molecules of 5a, which coincided
with the result of the elemental analysis of 5a. Two sym-
metrically independent molecules of 5a found in the crys-
talline state are shown as an ORTEP drawing in
Figure 2.3b The N–C=N+–O– moiety is planar with Z-con-
The results presented below are an elaboration of the
study conducted by Zaleska and co-workers on building
2 ArNO
Ar
–O
Ar
HO
Ar
cat. 2 OH–
(a)
HO
N
N
N
NHHet
1
NHHet
1
Me
3
taut.
– AcOH
Me
NHHet
3
2
NHHet
2
N
HN
O
O
O
O
Ar
N
O
Ar
O
5a–e
46–82%
Ar
OH
4a–d
R
a: R = H, b: R = 4-Me, c: R = 5-Me, d: R = 5-NO2
a–d: Ar = Ph, e: Ar = 4-MeC6H4, R = 4-Me
Het =
N
Scheme 1 Reagents and conditions: (a) MeOH, r.t., 12 h.
SYNTHESIS 2008, No. 18, pp 2977–2985
x
x.
x
x
.
2
0
0
8
Advanced online publication: 22.08.2008
DOI: 10.1055/s-2008-1067236; Art ID: Z10108SS
© Georg Thieme Verlag Stuttgart · New York

2978
B. Trzewik et al.
PAPER
Figure 2 The mutual arrangements of two symmetrically indepen-
dent molecules of 5a (aromatic hydrogen atoms were removed for
clarity; non-hydrogen atom displacement ellipsoids are set at 10%
probability level). The values of C8–C10, C10–N11, and C10–N12
bond lengths are 151.1(3), 134.7(3), and 131.5(3) pm for (a) and
151.6(4), 134.3(3), and 131.1(3) pm for (b). The sum of valence an-
gles at C10 is 359.9(6)° for both (a) and (b). The N11–C10–N12–O13
torsion angles are: 2.6(3)° for (a) and –4.1(3)° for (b).
Figure 3 An ORTEP view of a molecule of 6a with the crystallo-
graphic atom numbering scheme (aromatic hydrogen atoms were re-
moved for clarity; non-hydrogen atom displacement ellipsoids are
drawn at 50% probability level). The values of the selected geometric
parameters are as follows: (a) bond lengths (pm): O1–N2 = 141.6(2),
N2–C3 = 138.7(2), C3–C4 = 153.5(2), C4–N5 = 136.9(2), N5–
C6 = 147.0(2), C6–O1 = 140.0(2), and C3–N3 = 126.3(2); (b) va-
lence angles (°): C6–O1–N2 = 106.5(1), O1–N2–C3 = 110.9(1), C4–
N5–C6 = 119.3(1), and C3–N3–C31 = 124.6(1); (c) torsion angles
(°): O1–N2–C3–C4 = –30.4(2), N2–C3–C4–N5 = –13.0(2), C3–C4–
N5–C6 = 16.8(2), C4–N5–C6–O1 = 22.7(2), N5–C6–O1–N2 = –
67.1(2), and C6–O1–N2–C3 = 73.1(2).
figuration with respect to the C10–N12 double bond,
which is slightly elongated, while the C10–N11 single
bond is shortened,3c both deviations being due to p-delo-
calisation. The values for the bond lengths led us to the
conclusion that only one mesomeric structure of 5a pre-
vailed, in contrast to (Z)-N-[(phenylamino)methyl-
ene]aniline oxide.3d All functional groups in 5a are
involved in intermolecular hydrogen N–H···O and N–
H···N type bonds, which stabilise the molecular structure
of 5a.
The presence of several nucleophilic centres in a-amido-
a-aminonitrones 5 allowed their use in dialkylation reac-
tions with alkyl dihalides. First we examined the reaction
with diiodomethane in anhydrous DMF. After adding two
equivalents of sodium hydride to the reaction mixture,
TLC indicated completion of the reaction in 1.5 hours.
Mass spectra (EI) of 5a–e showed very small peaks of mo-
lecular ions and distinctive peaks [M+– 16], arising from
the loss of the oxygen atom from 5 during fragmentation.
In MS(ESI) spectra of 5 [M+ + H] peaks constitute the
base (or even the only) peaks.
We expected the dialkylation to start on the nitrone oxy-
gen atom,2a and the proximity of the oxygen atom and the
amine NH group2a,3d suggested the possibility of 1,2,4-ox-
adiazole ring closure. However, the IR spectra of products
6a–c no longer exhibited NH amide bands above 3100
cm–1. That observation suggested that the methylene frag-
ment linked the nitrone oxygen atom and the amide nitro-
gen atom; hence 1,2,5-oxadiazin-4-ones 6a–c were
formed (Scheme 2). The structure of 1,2,5-oxadiazin-4-
one 6a was confirmed by a single crystal X-ray diffraction
experiment. An ORTEP view of a molecule of 6a is
shown in Figure 3. The molecule of 6a adopts a boat con-
formation with a pseudo mirror-plane cutting through O1,
C4, and O4 atoms.
We proposed a mechanism for the formation of 5a–e
(Scheme 1). After a base-catalysed attack of two mole-
cules of nitrosobenzene on C2 of 4a–d, a splitting of the
C2–C3 bonds takes place (acidic cleavage). The loss of a
molecule of acetic acid followed by a proton shift results
in the formation of nitrones 5a–e. Thus, a transformation
of 3-oxobutanoic acid derivatives into oxalic acid deriva-
tives takes place. It should be noted that the introduction
of a phenyl group in place of the methyl group at C3 of 4a
totally changes the reactivity of the corresponding py-
ridylide against nitrosobenzenes.6
–O
N
Ph
Ph
Ph
N
O
R = 4-Me, (b)
R = 5-NO2, (a)
N
N
N
H
N
H
N
(a)
Ph
N
H
N
N
H
52–70%
30–35%
R
O
R
Ph
O
N
N
R
O
Ph
6a–c
5a–d
a: R = H, b: R = 4-Me, c: R = 5-Me, d: R = 5-NO2
7b,d
Scheme 2 Reagents and conditions: (a) CH2I2, NaH (2 equiv), anhyd DMF, –10 °C→r.t, 1.5 h; (b) I(CH2)2I, NaH (2 equiv), anhyd DMF,
–10 °C→r.t, 1.5 h.
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York

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a-Amido-a-aminonitrone Building Blocks for Heterocyclic Systems
2979
The first synthesis of the 1,2,5-oxadiazine system was re-
ported in 1905,7a but it was later proved that the structure
of the products had been assigned incorrectly,7b so the ring
was probably obtained for the first time in 1930 by Busch
and Kaemmerer8a from (Z)-a-aminooximes and alde-
hydes.8b–e Diketones8f,g or acetals8h can be used instead of
aldehydes, and a-aminohydroxylamines can replace a-
aminooximes.8i There are also other methods,8j–q includ-
ing those based on reactions between: a-halooximes and
imines,8j nitrosoalkenes and imines,8k,l nitrones and allyl-
amines,8m also in a stereoselective manner.8n The system
can also be obtained through ring expansions.8r–w Diacy-
lations of both a-aminooximes9a–c and a-amino-
hydroxylamines9d,e lead to 6-oxo derivatives. 1,2,5-
Oxadiazines have been used for obtaining imidazole de-
rivatives.9d,f The N–O bond in 1,2,5-oxadiazines can be
easily broken, which leads to various products,8e,o,9d,f,g
such as vicinal diamines (an example of indirect amina-
tion of alkenes).8m,n
Figure 4 An ORTEP view of 8a with the crystallographic atom
numbering scheme (aromatic hydrogen atoms were removed for cla-
rity; non-hydrogen atom displacement ellipsoids are drawn at 50%
probability level). The values of the selected geometric parameters
are as follows: (a) bond lengths (pm): N2–C1 = 134.0(2), C1–
O1 = 124.1(2), C1–C2 = 149.4(2), C2–N4 = 129.0(2), and C2–
N3 = 136.4(2); (b) valence angles (°): C21–N2–C1 = 123.9(1), C2–
N3–C31 = 130.2(1), and C26–N4–C2 = 118.2(1); (c) torsion angles
(°): C32–C31–N3–C2 = –171.3(2) and C31–N3–C2–N4 = –3.0(2).
The reaction of 5b with 1,2-diiodoethane did not yield the
expected 1,2,5-oxadiazepan-4-one, but amidine 7b, i.e.
deoxygenation took place. The IR spectra of 7a showed
two strong NH bands between 3400 and 3200 cm–1 and a
C=O band at about 1700 cm–1. The NMR spectra did not
indicate the presence of an ethylene group. The mass
spectrum of 7b showed a molecular peak with its m/z low-
ered by 16 compared with 5b. The result of the elemental
analysis was in agreement with the proposed structure of
7b. It should be noted that 5d, possessing a strong elec-
tron-withdrawing nitro group in the pyridine ring, gave 7d
instead of 6d in the reaction with methylene diiodide.
Such examples of deoxygenation of nitrones are relatively
rare.10
Amidines11a of type 7b and 7d are interesting as building
blocks because their molecules contain both amidine and
amide moieties,11b and allow both electrophilic and nu-
cleophilic reactions. The number of methods for preparing
such compounds is limited;11 derivatives of oxalic11c,i–l or
acetic11b,g,h,j–l acids have mostly been used as starting ma-
terials. We proposed a method for preparing such com-
pounds from 3-oxobutanoic acid derivatives.
rivatives have recently been investigated as potential gly-
cogen phosphorylase inhibitors.12d An ORTEP view of the
8a molecule with crystallographic atom numbering
scheme is shown in Figure 4.
The whole molecule of 8a is essentially planar. The posi-
tions of the hydrogen atoms at N2 and N3 were found on
the basis of Fourier difference maps and confirmed by the
values of the corresponding valence angles at the nitrogen
atoms. The hydrogen atoms are involved in hydrogen
bonds: one linear intermolecular (N2–H2···O1; –x, –y, –z)
and one intramolecular (N3–H3···O1).
In reactions with 2-aminobenzylamine, naphthalene-1,3-
diamine, and biphenyl-2,2¢-diamine, the amide moieties
of nitrones 5a–d were left unaffected; the processes con-
sisted of binucleophilic attack on C-2 carbon atoms of ni-
trones 5a–d, leading to derivatives of quinazoline 9a,
perimidine 10a–d, and dibenzo[d,f][1,3]diazepine 11a–d
(Scheme 3).
a-Amido-a-aminonitrones 5a–d were then used as bielec-
trophilic reagents in heterocyclisation reactions with aro-
matic 1,2-, 1,3-, and 1,4-diamines. In these reactions, the
nitrone moieties acted as active equivalents of carbonyl
groups.1c,l–n,2a The reaction of 5a with o-phenylenedi-
amine yielded the known12a–c 3-(phenylamino)quinoxa-
lin-2(1H)-one 8a (mp 253.0–254.0 °C). One o-
phenylenediamine amine group replaces the nitrone moi-
ety of 5a and the second transaminates the amide moiety,
resulting in the formation of 8a.2a This compound has
been reported in two different tautomeric forms,12a–c with
melting points of 25212a and 247–248 °C.12b,c The small
differences between the melting points of 8a, A, and B
suggested that their structures may be the same, at least in
the solid state. An X-ray diffraction analysis confirmed
the structure of the obtained quinoxaline derivative as 8a.
Determining its structure should prove useful, since its de-
1
The H NMR spectra of all compounds depicted in
Scheme 3 contain singlets from the NH groups of the
amide moieties in the range d = 10.89–9.84 ppm. Both MS
(EI) and elemental analyses supported the proposed struc-
tures. The structure of 11b was unambiguously deter-
mined by single crystal structure analysis.16
The first synthesis of 5H-dibenzo[d,f][1,3]diazepine was
reported in 1932 by Sako.13a,b The vast majority of other
methods involve reactions of biphenyl-2,2¢-diamine with
1,1-bielectrophilic reagents such as cyanogen bromide
(BrCN),13c ethyl benzimidate hydrochloride,13d,e benzoni-
trile,13f or methyl arylcarbimidothioates.13g A review of
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2980
B. Trzewik et al.
PAPER
N
amide
amide
(a)
amide
N
NH
–O
Ph
O
58%
N
9a
N
(c)
H
N
amide
HN
55–69%
NH
(b)
N
R
Ph
45–74%
NH
5a–d
11a–d
10a–d
a: R = H, b: R = 4-Me, c: R = 5-Me, d: R = 4-NO2
Scheme 3 Reagents and conditions: (a) MeCN, 2-aminobenzylamine (2 equiv), TsOH (cat), reflux, 2 h; (b) MeCN, naphthalene-1,8-diamine
(2 equiv), TsOH (cat), reflux, 2 h; (c) MeCN, biphenyl-2,2¢-diamine, TsOH (cat), reflux, 2 h.
a Finnigan MAT 95S apparatus at an ionisation potential of 70 eV.
MS (ESI) spectra were recorded on an Esquire 3000 mass spectrom-
eter; the samples were solved in a MeOH–CHCl3 mixture and anal-
ysed in the positive-ion mode. Elemental analyses (CHN) were
carried out using a Euro-EA 3018 analyser. X-ray diffraction data
were collected with a Nonius Kappa CCD diffractometer using
MoKa radiation (l = 0.71073 Å)17a,b at 293(2) K. The structures
were solved by SIR9217c and refined by SHELXL9717d programs.
the methods available for preparing diazepines was made
by Herr.13h
The 1H-perimidine system has been known since 1874,
when it was obtained by de Aguiar.14a Transformations
leading to perimidines start with 1,8-naphthalenediamine
(NDA) as substrate and most consist of reactions with
bielectrophilic reagents, e.g.: aldehydes,14b–e acyl chlo-
rides,14f di- or tetracyanoethylene derivatives,14g aryl an-
hydrides,14h cyanamide,14i isothiocyanates,14h or ortho-
formates.14j 2,3-Dihydro-1H-perimidines can be obtained
from NDA and aldehydes14k or by oxidation of NDA by
manganese dioxide (MnO2).14l Perimidines can act as sub-
strates in reactions leading to more condensed
systems14f,g,m such as 1,3-diazapyrenes14m or pyri-
do[1,2,3-cd]perimidines.14f
Yields are given for pure products. Silica gel for column chroma-
tography was purchased from Fluka (Silica gel 60, 70–230 mesh
ASTM, activity 2–3 according to Brockmann, Schodder). TLC
plates were purchased from Fluka (thickness 0.2 mm, pore diameter
60 Å, with 254 nm fluorescent indicator). NaH was used as 55–60%
suspension in mineral oil. 4-Methylnitrosobenzene was prepared
according to the previously reported procedure.18
(N-Pyridyn-2-yl)acetoacetamides (4a–d); General Procedure
A solution of ethyl acetylacetate (17.3 mL, 0.1 mol) in xylene (70
mL) was heated to reflux. To the boiling mixture, the corresponding
aminopyridine (0.1 mol) was added in portions over 1 h, and the lib-
erated EtOH was distilled off. The remaining traces of EtOH were
co-distilled with xylene (20 mL). Cooling the mixture to 0 °C yield-
ed the products, which were suction-filtered off in pure form.
Recent syntheses of quinazolines were based either on the
addition of Grignard reagents to dicyjanoanilines,15a or the
Biginelli reactions.15b Quinazolines can also be obtained
from dimethoxybenzenes15c or cyanoaromatic com-
pounds,15d and various aldehydes.15e,f
It should be stressed that compounds 11a–d are, to the
best of our knowledge, the first examples of 5H-diben-
zo[d,f][1,3]diazepine-6-carboxylic acid derivatives.
3-Oxo-N-pyridyn-2-ylbutanamide (4a)
Yield: 14.2 g (80%); colourless needles; mp 113.0–114.0 °C.3
N-(4-Methylpyridin-2-yl)-3-oxobutanamide (4b)
Yield: 14.2 g (74%) (Lit.19 yield: 75%); colourless needles; mp
122.0–123.0 °C (Lit.19 122–123 °C).
In conclusion, reaction N-pyridin-2-ylamides of 3-oxobu-
tyric acid and nitrosobenzene provided a-amido-a-amino-
nitrones 5a–e in good yields, which were used as diverse
building blocks for constructing heterocyclic rings. In di-
alkylation reactions, the relatively rare 1,2,5-oxadiazinan-
4-one derivatives 6a–d were obtained. In some cases
amidines 7 were formed. Reactions of 5a–d with aromatic
1,2-, 1,3-, and 1,4-diamines yielded derivatives of 3,4-di-
hydroquinoxalin-2(1H)-one 8a, 3,4-dihydroquinazoline
9a, 1H-perimidine 10a–d, and 5H-dibenzo[d,f][1,3]diaz-
epine 11a–d, respectively. All the products, with the ex-
ception of 8a, contain N-pyridin-2-ylocarboxamide
substituents, which may prove valuable for pharmacolog-
ical uses.
N-(5-Methylpyridin-2-yl)-3-oxobutanamide (4c)
Yield: 10.9 g (57%) (Lit.19 yield: 78%); colourless needles; mp
162.0–163.0 °C (Lit.19 152–153 °C).
N-(5-Nitropyridin-2-yl)-3-oxobutanamide (4d)
Yield: 16.0 g (72%); light-yellow powder; mp 173.0–174.0 °C.
IR (KBr): 3248, 3206, 3148, 1714, 1692, 1674, 1347, 1315 cm–1.
1H NMR (CDCl3): d (keto form; 82%) = 9.91 (s, 1 H, NH), 9.17 (dd,
J = 2.7, 0.6 Hz, 1 H, ArH-6), 8.49 (ddd, J = 9.0, 2.7, 0.6 Hz, 1 H,
ArH-4), 8.35 (dd, J = 9.0, 0.6 Hz, 1 H, ArH-3), 3.67 (s, 2 H, CH2),
2.36 (s, 3 H, CH3); d (enol form; 18%) = 13.20 (s, 1 H, OH), 9.12
(dd, J = 2.7, 0.6 Hz, 1 H, ArH-6), 8.47 (ddd, J = 9.0, 2.7, 0.6 Hz,
1 H, ArH-4), 8.38 (dd, J = 9.0, 0.6 Hz, 1 H, ArH-3), 7.91 (s, 1 H,
CH), 5.08 (d, J = 0.3 Hz, 1 H, NH), 2.03 (s, 3 H, CH3).
13C NMR (CDCl3): d (keto form; 82%) = 203.5 (COCH3), 164.4
(CONH), 154.8 (ArC-5), 144.8 (ArC-6), 140.8 (ArC-2), 134.0
(ArC-4), 113.3 (ArC-3), 49.8 (CH2), 31.3 (CH3); d (enol form;
18%) = 91.3 (CH), 21.8 (CH3).
Melting points were determined on an Electrothermal IA9000 digi-
tal melting point apparatus and are uncorrected. IR spectra were ob-
tained on a Bruker IFS 48 spectrometer. 1H and 13C NMR spectra
were recorded with a Bruker Avance II 300 spectrometer at 300.18
and 75.48 MHz, respectively, at 300 K. MS (EI) were recorded on
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York

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a-Amido-a-aminonitrone Building Blocks for Heterocyclic Systems
2981
MS (EI): m/z (%) = 223 (23) [M+], 208 (23) [M+ – CH3], 180 (13)
13C NMR (CD3OD): d = 158.2 (NCN), 149.3 (CONH), 143.8,
[M+ – CH3CO], 166 (19) [O2N-C5H3N-NHCO+], 139 (100) [O2N-
139.9, 132.1, 130.4, 130.3, 126.9, 125.9, 123.8, 115.1, 17.8 (CH3).
C5H3N-NH2 ], 123 (8) [O2N-C5H3N+], 109 (21).
+
MS (EI): m/z (%) = 192 (26) [M+ – 2 Ph], 177 (17) [M+ – 2 Ph –
CH3], 135 (11) [H3C-C6H3N-NHCO+], 108 (100) [PhNOH+], 107
(17) [H3C-C6H3N-NH+, PhNO+].
Anal. Calcd for C9H9N3O4: C, 48.43; H, 4.06; N, 18.83. Found: C,
48.42; H, 3.88; N, 18.86.
MS (ESI): m/z = 347 [M+ + H].
2-Anilino-2-[oxido(phenyl)imino]-N-pyridin-2-ylacetamides
(5a–e); General Procedure
Anal. Calcd for 2C20H18N4O2·CH3OH: C, 67.94; H, 5.56; N, 15.46.
Found: C, 68.10; H, 5.86; N, 15.94.
A suspension of the corresponding 3-oxo-(N-pyridyn-2-yl)butan-
amide 4a–d (0.01 mol), the corresponding nitrosobenzene (0.02 mol)
and NaOH (0.02 g) in MeOH (15 mL) was stirred at r.t. The mixture
turned brown, clarified and warmed up to 40 °C after several min-
utes. After 30 min, white (yellow in the case of 5d) powder of the
product started to precipitate. The suspension was stirred overnight
and the product was collected by suction-filtration and washed with
small amount of cold MeOH.
(Z)-2-Anilino-2-[oxido(phenyl)imino]-N-(4-nitropyridin-2-
yl)acetamide (5d)
Yield: 2.20 g (58%); light-yellow powder; mp 140.0–141.0 °C.
IR (KBr): 3495, 3367, 1696, 1417, 1396, 1347 cm–1.
1H NMR (CD3OD): d = 9.04 (d, J = 1.8 Hz, 1 H, ArH-6), 8.46 (dd,
J = 9.3, 3.0 Hz, 1 H, ArH-4), 8.00 (d, J = 8.7 Hz, 1 H, ArH-3), 7.58
(d, J = 7.2 Hz, 2 H), 7.43–7.20 (m, 7 H), 7.14 (t, J = 7.2 Hz, 1 H).
13C NMR (CD3OD): d = 155.7 (NCN), 147.6, 145.8, 143.8, 142.6,
135.1, 134.0, 130.3, 126.8, 125.5, 123.9, 114.3, 108.6.
(Z)-2-Anilino-2-[oxido(phenyl)imino]-N-pyridin-2-ylacetamide
(5a)
Yield: 2.70 g (81%); white powder; mp 152.0–153.0 °C.
MS (EI): m/z (%) = 377 (3) [M+], 361 (18) [M+ – O], 211 (19)
IR (KBr): 3363, 3108, 1683 cm–1.
[PhN(OH)-C=NPh+], 195 (35) [PhNH-C=NPh+], 166 (86) [O2N-
1H NMR (CD3OD): d = 8.19 (d, J = 4.2 Hz, 1 H, ArH-6), 7.71 (d,
J = 8.4 Hz, 1 H), 7.65 (dd, J = 7.8, 1.2 Hz, 1 H), 7.58 (d, J = 7.5 Hz,
2 H), 7.44–7.27 (m, 7 H), 7.13 (tt, J = 6.4, 2.4 Hz, 1 H), 7.06 (t,
J = 5.8 Hz, 1 H).
C6H3N-NHCO+], 139 (22) [O2N-C6H3N-NH2 ], 120 (30) [C5H3N-
+
NHCO+].
MS (ESI): m/z = 378 [M+ + H].
13C NMR (CD3OD): d = 158.5 (NCN), 151.5 (CONH), 149.4,
143.8, 139.5, 130.3, 130.3, 126.9, 125.8, 123.8, 122.1, 115.5.
Anal. Calcd for 2C19H15N5O4·CH3OH: C, 59.54; H, 4.36; N, 18.30.
Found: C, 59.40; H, 4.04; N, 18.80.
MS (EI): m/z (%) = 332 (3) [M+], 316 (29) [M+ – O], 241 (10) [M+
– PhN], 225 (33) [M+ – O – PhN], 195 (35) [PhN=CNHPh+], 121
(96) [C5H4N-NHCO+], 107 (34) [PhNO+].
(Z)-2-Anilino-2-[oxido(4-methylphenyl)imino]-N-(4-methylpy-
ridin-2-yl)acetamide (5e)
Yield: 1.04 g (46%); white powder; mp 123.0–124.0 °C.
IR (KBr): 3132, 1686 cm–1.
MS (ESI): m/z = 333.2 [M+ + H].
Anal. Calcd for 2C19H16N4O2·CH3OH: C, 67.23; H, 5.21; N, 16.08.
Found: C, 67.65; H, 5.03; N, 16.40.
1H NMR (CD3OD): d = 8.04 (d, J = 4.8 Hz, 1 H, ArH-6), 7.56 (s,
1 H, ArH-3), 7.44 (d, J = 7.8 Hz, 2 H), 7.21 (d, J = 7.8 Hz, 2 H),
7.16 (d, J = 8.4 Hz, 2 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.91 (d, J = 4.8
Hz, 1 H), 2.31 (s, 3 H, CH3), 2.26 (br s, 6 H, 2 × CH3).
13C NMR (CD3OD): d = 158.1 (NCN), 151.5 (CONH), 148.9,
141.2, 137.3, 136.1, 130.9, 125.9, 124.1, 123.1, 116.0, 21.2 (CH3),
20.9 (CH3).
MS (EI): m/z (%) = 374 (0.6) [M+], 358 (8) [M+ – O], 269 (7) [M+
– H3C-C6H4-N], 135 (100) [H3C-C6H3N-NHCO+], 107 (45) [H3C-
C6H3N-NH+].
(Z)-2-Anilino-2-[oxido(phenyl)imino]-N-(4-methylpyridin-2-
yl)acetamide (5b)
Yield: 2.85 g (82%); white powder; mp 148.0–149.0 °C.
IR (KBr): 3207, 3064, 1680, 1419 cm–1.
1H NMR (CD3OD): d = 8.03 (d, J = 4.8 Hz, 1 H, ArH-6), 7.58 (d,
J = 7.8 Hz, 2 H), 7.56 (s, 1 H, ArH-3), 7.44–7.27 (m, 7 H), 7.14 (tt,
J = 6.6, 1.8 Hz, 1 H), 6.29 (d, J = 4.8 Hz, 1 H, ArH-5), 2.25 (s, 3 H,
CH3).
13C NMR (CD3OD): d = 158.4 (NCN), 151.5 (CONH), 148.9,
148.4, 143.8, 130.3, 126.9, 125.8, 123.8, 123.1, 116.0, 21.2 (CH3).
MS (EI): m/z (%) = 346 (1.5) [M+], 330 (23) [M+ – O], 238 (8) [M+
– PhNOH], 211 (6) [M+ – H3C-C6H3N-NHCO], 135 (100) [H3C-
C6H3N-NHCO+], 108 (41) [PhNOH+].
MS (ESI): m/z = 347.2 [M+ + H], 239.1, 213.0 [M+ + H – CH3-
C5H3N-NHCO], 195 [diphenylcarbodiimide moiety], 135 [CH3-
C5H3N-NHCO+].
MS (ESI): m/z = 375 [M+ + H].
Anal. Calcd for 2C22H22N4O2·CH3OH: C, 69.21; H, 6.20; N, 14.35.
Found: C, 69.56; H, 6.26; N, 14.73.
(E)-2-Phenyl-3-(phenylimino)-5-pyridin-2-yl-1,2,5-oxadiazi-
nan-4-ones (6a–c); General Procedure
A solution of the corresponding (Z)-2-[oxido(phenyl)imino]-2-
(phenylamino)-(N-pyridin-2-yl)ethanamide 5a–d (1.5 mmol) in an-
hydrous DMF (10 mL) was cooled in an ice-bath to –10 °C. CH2I2
(0.40 g, 0.12 mL, 1.5 mmol) was added with stirring and the flask
was closed with a tube filled with CaCl2. NaH (0.063 g, 1.5 mmol)
was added in two portions to the stirred mixture over 30 mins. Fur-
ther NaH (0.063 g, 1.5) was then added and the ice-bath removed
(the reaction was monitored by TLC). After 1 h the reaction mixture
was evaporated to dryness under reduced pressure (10 mm Hg) to
remove DMF completely. The brown residue was immediately
chromatographed (CDCl3–MeOH, 40:1) and the second fraction
yielded the product as yellow prisms. The product was recrystal-
lised from MeOH.
Anal. Calcd for 2C20H18N4O2·CH3OH: C, 67.94; H, 5.56; N, 15.46.
Found: C, 67.79; H, 5.41; N, 15.64.
(Z)-2-Anilino-2-[oxido(phenyl)imino]-N-(5-methylpyridin-2-
yl)acetamide (5c)
Yield: 1.97 g (57%); white powder; mp 136.0–137.0 °C.
IR (KBr): 3165, 1694, 1383, 1306 cm–1.
1H NMR (CD3OD): d = 8.03 (dd, J = 1.5, 0.8 Hz, 1 H, ArH-6),
7.60–7.56 (m, 2 H), 7.49–7.24 (m, 9 H), 7.14 (tt, J = 6.6, 1.8 Hz,
1 H), 2.22 (s, 3 H, CH3).
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York

2982
B. Trzewik et al.
PAPER
(E)-2-Phenyl-3-(phenylimino)-5-(pyridin-2-yl)-1,2,5-oxadiazi-
nan-4-one (6a)
13C NMR (CDCl3): d = 161.5, 151.2, 150.5, 148.6, 146.7, 141.1,
137.3, 128.6, 128.6, 125.1, 123.8, 123.4, 122.0, 115.0, 22.1 (CH3).
Yield: 0.36 g (70%); yellow prisms; mp 122.5–123.5 °C.
IR (KBr): 2925 (CH2), 2855 (CH2), 1697 (CO) cm–1.
MS (ESI): m/z = 331.2 [M+ + H], 330.2, 316.3 [M+ + H – CH3],
135.0 [CH3-C5H3N-NHCO+].
1H NMR (CDCl3): d = 8.37 (ddd, J = 4.9, 2.0, 0.9 Hz, 1 H), 7.78 (td,
J = 8.0, 2.0 Hz, 1 H), 7.69 (m, 1 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.21
(tt, J = 7.5, 1.2 Hz, 1 H), 7.15–7.09 (m, 3 H), 6.96 (t, J = 7.5 Hz,
2 H), 6.94–6.86 (m, 1 H), 6.81 (d, J = 7.5 Hz, 2 H), 6.67 (d, J = 7.5
Hz, 1 H), 6.07 (s, 2 H, CH2).
Anal. Calcd for C20H18N4O: C, 72.71; H, 5.49; N, 16.96. Found: C,
72.80; H, 5.46; N, 16.86.
N-(5-Nitropyridin-2-yl)-2-(phenylamino)-2-(phenylimino)eth-
anamide (7d)
Yield: 0.16 g (30%); yellow needles; mp 176.0–178.0 °C.
IR (KBr): 3312 (NH), 3271 (NH), 1704 (CONH) cm–1.
1H NMR (CDCl3): d = 10.98 (s, 1 H, CONH), 9.24 (dd, J = 2.7, 0.6
Hz, 1 H, PyH-6), 8.57 (dd, J = 9.0, 2.7 Hz, 1 H, PyH-4), 8.50 (dd,
J = 9.0, 0.6 Hz, 1 H, PyH-3), 8.34 (s, 1 H, NH), 7.00–6.95 (m, 4 H,
PhH), 6.93 (t, J = 7.2 Hz, 1 H, PhH), 6.81 (t, J = 7.2 Hz, 1 H, PhH),
6.67 (d, J = 7.8 Hz, 2 H, PhH), 6.66 (d, J = 7.8 Hz, 1 H, PhH).
13C NMR (CDCl3): d = 158.7, 157.4, 151.4, 149.0, 148.1, 139.0,
138.8, 129.3, 129.3, 128.7, 123.4, 120.5, 119.1, 117.9, 114.4, 81.2
(CH2).
MS (ESI): m/z = 345.2 [M+ + H].
Anal. Calcd for C20H16N4O2: C, 69.76; H, 4.68; N, 16.27. Found: C,
69.81; H, 4.84; N, 16.58.
(E)-5-(4-Methylpyridin-2-yl)-2-phenyl-3-(phenylimino)-1,2,5-
oxadiazinan-4-one (6b)
13C NMR (CDCl3): d = 162.2, 155.1, 146.2, 145.7, 141.5, 140.4,
136.8, 134.7, 128.8, 128.7, 125.5, 124.3, 123.5, 122.0, 113.4.
Yield: 0.28 g (52%); yellow prisms; mp 141.0–143.0 °C.
IR (KBr): 2941, 2921, 1698 (CO) cm–1.
MS (ESI): m/z = 362.2 [M+ + H], 330.2 [M+ + H – 2 × O], 316.3 [M+
+ H – NO2].
1H NMR (CDCl3): d = 8.22 (dd, J = 5.1, 0.5 Hz, 1 H), 8.03 (br s,
1 H), 7.69 (br s, 1 H), 7.39 (br s, 1 H), 7.22 (br s, 4 H), 7.03–6.99
(m, 1 H), 6.95 (d, J = 4.8 Hz, 2 H), 6.82 (dd, J = 8.4, 1.2 Hz, 2 H),
6.05 (s, 2 H, CH2), 2.35 (s, 3 H, CH3).
13C NMR (CDCl3): d = 150.8, 149.6, 147.0, 128.6, 128.4, 128.0,
126.0, 122.7, 122.2, 121.4, 120.9, 118.4, 117.7, 80.6 (CH2), 21.3
(CH3).
Anal. Calcd for C19H15N5O3: C, 63.15; H, 4.18; N, 19.38. Found: C,
62.76; H, 3.91; N, 19.76.
Reactions of Nitrones 5a–d with Aromatic and Aliphatic-
Aromatic Diamines; General Procedure
A solution of the corresponding 2-[oxido(phenyl)imino]-2-(phenyl-
amino)-N-(pyridin-2-yl)ethanamide 5a–d (1 mmol), the corre-
sponding diamine (2 mmol) [or biphenyl-2.2¢-diamine (1 mmol,
0.18 g)], and catalytic TsOH (0.01 g) in acetonitrile (10 mL) was
heated under reflux for 2 h. After cooling the mixture, the product
was collected by suction-filtration.
MS (ESI): m/z = 359.2 [M+ + H], 135 [H3C-C5H3N-NHCO+].
Anal. Calcd for C21H18N4O2: C, 70.38; H, 5.06; N, 15.63. Found: C,
70.62; H, 4.92; N, 15.85.
3-(Phenylamino)quinoxalin-2-(1H)-one (8a)
Yield: 0.18 g (75%); yellow needles; mp 253.0–254.0 °C.
IR (KBr): 3371 (NH), 1671 (CONH) cm–1.
1H NMR (DMSO-d6): d = 12.44 (s, 1 H, NH), 9.36 (s, 1 H, CONH),
8.15 (d, J = 8.1 Hz, 2 H), 7.52–7.49 (m, 1 H), 7.36 (t, J = 8.1 Hz,
2 H), 7.23–7.17 (m, 3 H), 7.05 (t, J = 7.3, 1 H).
13C NMR (DMSO-d6): d = 151.4 (CONH), 147.1 (C=N), 139.4,
132.2, 128.4, 128.4, 125.3, 124.7, 123.4, 122.5, 119.6, 114.9.
(E)-5-(5-Methylpyridin-2-yl)-2-phenyl-3-(phenylimino)-1,2,5-
oxadiazinan-4-one (6c)
Yield: 0.30 g (56%); yellow prisms; mp 136.0–138.0 °C.
IR (KBr): 2947, 2923, 1693 (CO) cm–1.
1H NMR (CDCl3): d = 8.18 (dd, J = 1.6, 0.8 Hz, 1 H), 7.68 (dd,
J = 8.7, 1.2 Hz, 1 H), 7.62 (ddd, J = 16.5, 2.2, 0.8 Hz, 1 H), 7.46–
7.36 (m, 2 H), 7.24–7.18 (m, 2 H), 7.13–7.06 (m, 2 H), 6.99–6.91
(m, 2 H), 6.80 (d, J = 7.4 Hz, 2 H), 6.04 (s, 2 H, CH2), 2.32 (s, 3 H,
CH3).
13C NMR (CDCl3): d = 148.5, 147.9, 147.4, 138.7, 129.2, 128.7,
128.6, 128.3, 126.1, 124.2, 119.8, 16.7, 113.3, 78.7 (CH2), 17.8
(CH3).
MS (EI): m/z (%) = 237 (96) [M+], 236 (100) [M+ – H], 208 (31)
[M+ – CHO], 134 (10) [C6H4(NH)NHCO+].
N-(Pyridin-2-yl)-3,4-dihydroquinazoline-2-carboxamide (9a)
Yield: 0.15 g (58%); yellow needles; mp 129.0–131.0 °C.
MS (ESI): m/z = 359.2 [M+ + H], 343.3 [M+ + H – O].
IR (KBr): 3335 (br, NH), 2998 (CH2), 2845 (CH2), 1691 (CONH)
cm–1.
Anal. Calcd for C21H18N4O2: C, 70.38; H, 5.06; N, 15.63. Found: C,
69.91; H, 5.00; N, 15.88.
1H NMR (CDCl3 + DMSO-d6): d = 9.84 (s, 1 H, CONH), 8.91 (t,
J = 6.3 Hz, 1 H, NH), 7.66 (d, J = 1.2 Hz, 1 H), 7.63 (d, J = 0.9 Hz,
1 H), 7.26 (dt, J = 7.5, 1.8 Hz, 1 H), 7.24 (dt, J = 8.4, 1.8 Hz, 1 H),
7.11 (dd, J = 7.5, 1.5 Hz, 1 H), 7.05 (tt, J = 7.5, 1.2 Hz, 1 H), 6.97
(td, J = 7.5, 1.5 Hz, 1 H), 6.62 (dd, J = 8.2, 0.9 Hz, 1 H), 6.56 (td,
J = 7.4, 1.2 Hz, 1 H), 4.32 (d, J = 6.3 Hz, 2 H, CH2).
2-(Phenylamino)-2-(phenylimino)-N-(pyridin-2-yl)ethan-
amides 7b and 7d; General Procedure
In the case of 7d the procedure was analogous to that used for the
synthesis of 6a–c. In the case of 7b, 1,2-diiodoethane (0.42 g, 1.5
mmol) was used in place of diiodomethane.
13C NMR (CDCl3 + DMSO-d6): d = 159.7, 157.2, 144.9, 136.4,
N-(4-Methylpyridin-2-yl)-2-(phenylamino)-2-(phenylimi-
no)ethanamide (7b)
Yield: 0.17 g (35%); light-yellow needles; mp 163.5–164.5 °C.
IR (KBr): 3330 (NH), 3158 (NH), 2925 (CH3), 1702 (CONH) cm–1.
1H NMR (CDCl3): d = 10.54 (s, 1 H, CONH), 8.42 (br s, 1 H, NH),
8.23 (d, J = 5.1 Hz, 1 H), 8.14–8.13 (m, 1 H), 6.98–6.92 (m, 5 H),
6.88 (t, J = 7.2 Hz, 1 H), 6.78 (t, J = 7.4 Hz, 1 H), 6.68–6.65 (m,
4 H), 2.42 (s, 3 H, CH3).
130.3, 128.2, 128.2, 124.2, 120.8, 119.5, 119.5, 116.9, 115.2.
MS (EI): m/z (%) = 252 (100) [M+], 251 (75) [M+ – H], 132 (72)
[3,4-dihydroquinazoline moiety + H], 131 (44) [3,4-dihydro-
quinazoline moiety], 121 (44) [C5H4N-NHCO+], 104 (18), 95 (10),
78 (35), 77 (13).
Anal. Calcd for C14H12N4O: C, 66.65; H, 4.79; N, 22.21. Found: C,
66.10; H, 4.68; N, 22.22.
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York

PAPER
a-Amido-a-aminonitrone Building Blocks for Heterocyclic Systems
2983
N-Pyridin-2-yl-1H-perimidine-2-carboxamide (10a)
Yield: 0.18 g (61%); dark-red needles; mp 222.0–225.0 °C.
1 H), 8.32 (tt, J = 9.9, 0.6 Hz, 1 H), 7.83 (dt, J = 8.7, 1.6 Hz, 1 H),
7.39 (t, J = 7.8 Hz, 1 H), 7.20–7.08 (m, 3 H), 6.72 (td, J = 3.0, 0.6
Hz, 1 H).
13C NMR (DMSO-d6): d = 159.5 (CONH), 157.1, 153.8, 151.3,
146.2, 144.9, 141.7, 138.2, 137.3, 135.1, 134.8, 134.5, 128.7, 124.8,
120.5, 113.4, 112.6.
IR (KBr): 3307 (NH), 1688 (C=O), 1631, 1575, 1539 (C=N), 1435,
1370, 1306 cm–1.
1H NMR (DMSO-d6): d = 11.14 (s, 1 H, NH), 10.01 (s, 1 H,
CONH), 8.41 (ddd, J = 4.9, 1.9, 0.9 Hz, 1 H), 8.15 (d, J = 8.5 Hz,
1 H), 7.92 (td, J = 7.9, 1.8 Hz, 1 H), 7.24 (ddd, J = 7.9, 4.9, 0.9 Hz,
1 H), 7.19 (t, J = 7.8 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.10 (d,
J = 8.0 Hz, 1 H), 7.04 (d, J = 8.5 Hz, 1 H), 6.76 (d, J = 7.0 Hz, 1 H),
6.66 (d, J = 7.0 Hz, 1 H).
13C NMR (DMSO-d6): d = 157.6 (CONH), 149.7, 148.4, 146.3,
143.1, 138.7, 137.4, 135.1, 128.7, 128.1, 122.9, 121.0, 120.5, 118.4,
114.6, 113.1, 104.0.
MS (EI): m/z (%) = 333 (54) [M+], 168 (12) [M+ – 5-NO2-2¢-Py-
+
NCO – H], 166 (100) [C11H6N2 , perimidinium], 140 (19)
[C10H6N+, benzoazepinium].
Anal. Calcd for C17H11N5O3: C, 61.26; H, 3.33; N, 21.01. Found: C,
61.30; H, 3.38; N, 20.97.
N-Pyridin-2-yl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide
(11a)
Yield: 0.21 g (65%); orange needles; mp 180.0–182.0 °C.
IR (KBr): 3273, 1687, 1489, 1433 cm–1.
MS (EI): m/z (%) = 288 (100) [M+], 168 (21) [M+ – 2-Py-NCO – H],
166 (82) [C11H6N2 (1H-perimidine moiety)], 140 (28) [C10H6N+,
benzoazepinium], 121 (12) [2-Py-NHCO+], 78 [C5H4N+].
Anal. Calcd for C17H12N4O: C, 70.82; H, 4.20; N, 19.43. Found: C,
70.55; H, 4.21; N, 19.83.
1H NMR (CDCl3): d = 10.25 (s, 1 H, CONH), 8.37 (ddd, J = 4.8,
1.8, 0.9 Hz, 1 H), 8.23 (dt, J = 8.4, 0.9 Hz, 1 H), 7.75 (td, J = 7.8,
1.6 Hz, 1 H), 7.61 (s, 1 H, NH), 7.29–7.02 (m, 8 H), 6.65 (dd,
J = 7.8, 1.2 Hz, 1 H).
N-(4-Methylpyridin-2-yl)-1H-perimidine-2-carboxamide (10b)
Yield: 0.17 g (55%); dark-red plates: mp 206.0–208.0 °C.
13C NMR (CDCl3): d = 158.9 (CONH), 150.8, 150.3 (2 × NC=N),
148.3, 146.8, 146.3, 138.4, 134.9, 130.3, 130.0, 129.9, 129.6, 129.2,
128.8, 127.7, 125.2, 120.3, 119.9, 113.7.
IR (KBr): 3329 (NH), 1704 (C=O), 1631, 1593, 1540 (C=N), 1469,
1447, 1370, 1302 cm–1.
1H NMR (DMSO-d6): d = 11.12 (s, 1 H, NH), 9.95 (s, 1 H, CONH),
8.26 (dd, J = 5.1, 0.3 Hz, 1 H), 7.99 (t, J = 0.8 Hz, 1 H), 7.22–7.06
(m, 5 H), 6.77 (d, J = 7.0 Hz, 1 H), 6.68 (d, J = 7.0 Hz, 1 H), 2.38
(s, 3 H, CH3).
13C NMR (DMSO-d6): d = 157.5 (CONH), 149.8, 149.5, 148.0,
146.3, 137.5, 135.1, 128.7, 128.1, 122.9, 121.5, 121.0, 118.5, 118.4,
114.6, 113.4, 104.0, 20.9 (CH3).
MS (EI): m/z (%) = 314 (72) [M+], 194 (100) [M+ – 2-Py-NCO],
167 (10) [C12H9N, carbazole moiety], 121 (24) [2-PyNHCO+], 78
(9) [C5H4N+].
Anal. Calcd for C19H14N4O: C, 72.60; H, 4.49; N, 17.82. Found: C,
72.75; H, 4.42; N, 18.05.
N-(4-Methylpyridin-2-yl)-5H-dibenzo[d,f][1,3]diazepine-6-car-
boxamide (11b)
Yield: 0.23 g (69%); orange needles; mp 203.0–204.0 °C.
IR (KBr): 3335, 3303, 3289, 1694, 1488, 1432 cm–1.
1H NMR (CDCl3): d = 10.21 (s, 1 H, CONH), 8.22 (d, J = 5.1 Hz,
1 H), 8.07 (t, J = 0.6 Hz, 1 H), 7.62 (s, 1 H, NH), 7.29 (d, J = 4.5
Hz, 1 H), 7.26 (dd, J = 5.4, 1.8 Hz, 1 H), 7.23 (dd, J = 3.8, 2.1 Hz,
1 H), 7.19 (dd, J = 3.0, 1.5 Hz, 1 H), 7.13 (td, J = 8.1, 1.2 Hz, 2 H),
7.05 (td, J = 7.8, 1.2 Hz, 1 H), 6.92 (ddd, J = 5.1, 0.6, 0.3 Hz, 1 H),
6.65 (dd, J = 7.8, 1.2 Hz, 1 H), 2.39 (s, 3 H, CH3).
MS (EI): m/z (%) = 302 (100) [M+], 168 (57) [M+ – 4-Me-2¢-Py-
+
NCO – H], 166 (72) [C11H6N2 , perimidinium], 140 (23) [C10H6N+,
benzoazepinium], 135 (36) [4-Me-2¢-Py-NHCO+], 92 (18) [4-Me-
C5H3N+].
Anal. Calcd for C18H14N4O: C, 71.51; H, 4.67; N, 18.53. Found: C,
71.40; H, 4.75; N, 18.42.
N-(5-Methylpyridin-2-yl)-1H-perimidine-2-carboxamide (10c)
Yield: 0.14 g (45%); dark-red needles; mp 244.0–245.0 °C.
IR (KBr): 3318 (NH), 1689 (C=O), 1631, 1594, 1544 (C=N), 1481,
1448, 1371, 1311 cm–1.
1H NMR (DMSO-d6): d = 11.12 (s, 1 H, NH), 9.94 (s, 1 H, CONH),
8.22 (dd, J = 1.6, 0.8 Hz, 1 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.72 (ddd,
J = 8.4, 1.2, 0.6 Hz, 1 H), 7.21–7.02 (m, 4 H), 6.74 (d, J = 6.9 Hz,
1 H), 6.66 (d, J = 6.9 Hz, 1 H), 2.27 (s, 3 H, CH3).
13C NMR (CDCl3): d = 158.9 (CONH), 150.9, 150.4, 149.9, 147.9,
146.8, 146.4, 134.9, 130.3, 130.0, 129.9, 129.6, 129.2, 128.8, 127.6,
125.2, 121.5, 119.8, 114.2, 21.4 (CH3).
MS (EI): m/z (%) = 328 (26) [M+], 194 (53) [M+ – 4-Me-2¢-Py-
NCO], 167 (5) [C12H9N+, carbazolium], 135 (24) [4-Me-2¢-PyNH-
CO+], 92 (81) [Me-C5H4N+], 91 (100).
13C NMR (DMSO-d6): d = 157.4 (CONH), 148.2, 147.5, 146.3,
143.1, 138.9, 137.5, 135.1, 129.7, 128.7, 128.1, 122.9, 120.9, 118.4,
114.5, 112.6, 104.0, 17.2 (CH3).
Anal. Calcd for C20H16N4O: C, 73.15; H, 4.91; N, 17.06. Found: C,
73.27; H, 4.89; N, 17.19.
N-(5-Methylpyridin-2-yl)-5H-dibenzo[d,f][1,3]diazepine-6-car-
boxamide (11c)
Yield: 0.18 g (57%); orange plates; mp 204.0–205.0 °C.
IR (KBr): 3303, 3267, 1681, 1487, 1435 cm–1.
1H NMR (CDCl3): d = 10.11 (s, 1 H, CONH), 8.10 (dd, J = 1.5, 0.6
Hz, 1 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.55 (s, 1 H, NH), 7.48 (dd,
J = 8.4, 2.1 Hz, 1 H), 7.21–7.09 (m, 4 H), 7.05 (td, J = 7.8, 1.2 Hz,
2 H), 6.97 (t, J = 7.3 Hz, 1 H), 6.57 (d, J = 7.8 Hz, 1 H), 2.24 (s,
3 H).
13C NMR (CDCl3): d = 158.8 (CONH), 151.0, 148.2, 148.2, 146.8,
146.4, 138.9, 134.9, 130.2, 130.0, 129.9, 129.8, 129.6, 129.2, 128.8,
127.6, 125.2, 119.9, 113.2, 17.9 (CH3).
MS (EI): m/z (%) = 302 (100) [M+], 168 (37) [M+ – 5-Me-2¢-Py-
+
NCO – H], 166 (59) [C11H6N2 , perimidinium], 140 (15) [C10H6N+,
benzoazepinium], 135 (10) [5-Me-2¢-Py-NHCO+].
Anal. Calcd for C18H14N4O: C, 71.51; H, 4.67; N, 18.53. Found: C,
71.46; H, 4.61; N, 18.18.
N-(5-Nitropyridin-2-yl)-1H-perimidine-2-carboxamide (10d)
Yield: 0.26 g (74%); dark-red needles; mp 243.0–244.0 °C.
IR (KBr): 3386 (NH), 3318 (NH), 1704 (C=O), 1632, 1580, 1542
(C=N), 1478, 1448, 1374, 1342, 1296 cm–1.
1H NMR (DMSO-d6): d = 10.98 (s, 1 H, NH), 10.89 (s, 1 H,
CONH), 9.24 (td, J = 2.2, 0.6 Hz, 1 H), 8.73 (dt, J = 9.3, 2.7 Hz,
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York

2984
B. Trzewik et al.
PAPER
Gilbert, B. C.; Atherton, N. M.; Davies, M. J., Eds.; RSC
Publishing: Cambridge, 1998, 116. (l) Boruah, M.; Konwar,
D.; Dutta, D. Indian J. Chem., Sect. B: Org. Chem. Incl.
Med. Chem. 2003, 42, 2112. (m) Freisleben, A.; Schieberle,
P.; Rychlik, M. J. Agric. Food Chem. 2002, 50, 4760.
(n) Saito, K.; Kawamura, A.; Kanie, T.; Ueda, Y.; Kondo, S.
Heterocycles 2001, 55, 1071.
MS (EI): m/z (%) = 328 (55) [M+], 194 (100) [M+ – 5-Me-2¢-Py-
NCO], 167 (6) [C12H9N+, carbazolium], 135 (25) [5-Me-2¢-PyNH-
CO+], 92 (6) [Me-C5H4N+].
Anal. Calcd for C20H16N4O: C, 73.15; H, 4.91; N, 17.06. Found: C,
73.16; H, 4.96; N, 17.17.
N-(5-Nitropyridin-2-yl)-5H-dibenzo[d,f][1,3]diazepine-6-car-
boxamide (11d)
Yield: 0.19 g (55%); red needles; mp 207.0–208.0 °C.
IR (KBr): 3341, 3287, 1708, 1498, 1437 cm–1.
(2) (a) Branco, P. S.; Prabhakar, S.; Lobo, A. M.; Williams, D.
J. Tetrahedron 1992, 48, 6335. (b) Warshaw, J. A.; Gallis,
D. E.; Acken, B. J.; Gonzalez, O. J.; Crist, D. R. J. Org.
Chem. 1989, 54, 1736. (c) Baiocchi, L.; Picconi, G.;
Palacco, G. J. Heterocycl. Chem. 1979, 16, 1477.
(d) Janzen, E. G.; Nutter, D. E. Magn. Reson. Chem. 1997,
35, 131. (e) Clement, B.; Kaempchen, T. Arch. Pharm.
(Weinheim, Ger.) 1987, 320, 566. (f) Szantay, C.; Szabo, L.
Chem. Ber. 1965, 98, 1013. (g) Aurich, H. G. Chem. Ber.
1968, 101, 1761.
(3) (a) Hodorowicz, M.; Stadnicka, K.; Trzewik, B.; Zaleska, B.
Acta Crystallogr., Sect. E 2008, 64, o599. (b) Farrugia, L. J.
J. Appl. Crystallogr. 1997, 30, 565. (c) Allen, F. H.;
Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A. G.;
Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, 1.
(d) Guimanini, A. G.; Toniutti, N.; Verardo, G.; Merli, M.
Eur. J. Org. Chem. 1999, 1, 141.
1H NMR (CDCl3): d = 10.53 (s, 1 H, CONH), 9.13 (dd, J = 2.4, 0.6
Hz, 1 H), 8.46 (dd, J = 9.0, 2.7 Hz, 1 H), 8.35 (td, J = 9.0, 0.3 Hz,
1 H), 7.40 (s, 1 H, NH), 7.22–6.97 (m, 7 H), 6.57 (dd, J = 7.8, 1.2
Hz, 1 H).
13C NMR (CDCl3): d = 159.4 (CONH), 154.2, 149.9, 146.4, 145.9,
145.0, 140.8, 134.9, 134.1, 130.4, 130.1, 129.8, 129.4, 128.9, 128.2,
125.5, 120.0, 112.7.
MS (EI): m/z (%) = 359 (78) [M+], 194 (100) [M+ – 5-NO2-2¢-Py-
NCO], 167 (15) [C12H9N+, carbazolium], 166 (18) [5-NO2-2¢-PyN-
HCO+], 139 (9) [NO2-C5H5N+], 120 (10) [C5H3N-NHCO+], 91 (7).
Anal. Calcd for C19H13N5O3: C, 63.51; H, 3.65; N, 19.49. Found: C,
63.38; H, 3.58; N, 19.60.
(4) (a) Zaleska, B.; Bazanek, T.; Socha, R.; Karelus, M.;
Grochowski, J.; Serda, P. J. Org. Chem. 2002, 67, 4526.
(b) Zaleska, B.; Socha, R.; Karelus, M.; Grochowski, J.;
Serda, P.; Szneler, E. J. Org. Chem. 2003, 68, 2334.
(c) Zaleska, B.; Trzewik, B.; Karelus, M.; Serda, P. J. Chem.
Res. 2007, 195. (d) Zaleska, B.; Socha, R. Monatsh. Chem.
2000, 131, 1061.
X-ray Crystallographic Data for 6a
Crystals suitable for the X-ray diffraction analysis were grown from
MeOH as yellow blocks. Empirical formula: C20H16N4O2; Formula
weight: 344.37; Crystal system = triclinic; Space group P1; Unit cell
dimensions: a = 7.2690(2) Å, b = 10.1355(3) Å, c = 12.9066(4) Å;
a = 67.916(2)°, b = 81.547(1)°, g = 80.982(1)°; V = 866.20(4) Å3;
z = 2; Dcalc = 1.320 Mg·m–3; F(000) = 360e; m(MoKa) = 0.089 mm–1.
(5) Zaleska, B.; Socha, R.; Ciechanowicz-Rutkowska, M.;
Pilati, T. Monatsh. Chem. 2000, 131, 1151.
(6) Zaleska, B.; Trzewik, B.; Stodolak, E.; Grochowski, J.;
Serda, P. Synthesis 2004, 2975.
(7) (a) Diels, O.; Leeden, R. Chem. Ber. 1905, 38, 3363.
(b) Wright, J. B. J. Org. Chem. 1964, 29, 1620.
Reflections
collected/unique/observed:
5309/3911/3165,
2s), wR2 = 0.1739,
R1 = 0.0550 (observed reflections,
I
>
S = 0.918.20
X-ray Crystallographic Data for 8a
(8) (a) Busch, R.; Kaemmerer, H. Chem. Ber. 1930, 63, 653.
(b) Gnihtel, H. Chem. Ber. 1970, 103, 3442. (c) Gnihtel, H.
Chem. Ber. 1971, 104, 1512. (d) Kiersznicki, T.; Rajca, A.
Pol. J. Chem. 1978, 52, 1827. (e) Kamitori, Y. Heterocycles
2000, 53, 107. (f) Amitina, S. A.; Grigor’ev, I. A.;
Tikhonov, A. Ya. Russ. Chem. Bull. 2006, 55, 1046.
(g) Tselinskii, I. V.; Mel’nikova, S. F.; Pirogov, S. V. Russ.
J. Org. Chem. 1997, 33, 1760. (h) Gnichtel, H.; Moeller, B.
Chem. Ber. 1981, 114, 3170. (i) Riddell, F. G.; Turner, E. S.
Tetrahedron 1979, 35, 1311. (j) Coskun, N.; Sümengen, D.
Synth. Commun. 1993, 23, 1699. (k) Marwaha, A.;
Bharatamb, P. V.; Mahajan, M. P. Tetrahedron Lett. 2005,
46, 8253. (l) Marwaha, A.; Singh, P.; Mahajan, M. P.
Tetrahedron 2006, 62, 5474. (m) Gravestock, M. B.;
Knight, D. W.; Malik, K. M. A.; Thornton, S. R. J. Chem.
Soc., Perkin Trans. 1 2000, 3292; and references cited
therein. (n) Gravestock, M. B.; Knight, D. W.; Thornton, S.
R. J. Chem. Soc., Chem. Commun. 1993, 169.
Crystals suitable for the X-ray diffraction analysis were grown from
MeOH as yellow plates. Empirical formula: C14H11N3O; Formula
weight: 237.26; Crystal system = monoclinic; Space group P21/c;
Unit cell dimensions: a = 14.1186(3) Å, b = 5.6424(1) Å,
c = 15.8454(5)
Å;
a = 90°,
b = 115.342(1)°,
g = 90°;
V = 1140.82(5) Å3; Z = 4; Dcalc = 1.381 Mg·m–3; F(000) = 496e;
m(MoKa) = 0.091 mm–1. Reflections collected /unique/observed:
3700/2608/1678, R1 = 0.0461 (observed reflections, I > 2s),
wR2 = 0.1294, S = 1.015.20
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e-mail: deposit@ccdc.cam.ac.uk].
Synthesis 2008, No. 18, 2977–2985 © Thieme Stuttgart · New York