A simple synthesis of 1-acyl-3-aryl-3H-pyrrolo[2′,3′:4,5]pyrimido[6,1-b]benzothiazol- 6-ium-2-olates: Betainic derivatives of a novel heterocyclic system

Article abstract of DOI:10.1055/s-2002-35992

The title compounds were obtained by acylation of 5-amino-1-aryl-4-(2-benzothiazolyl)-2,3-dihydro-2-pyrrolones with 3-fold excess of acid chlorides. Starting pyrrolones were prepared in high yields by alkylation of 2-benzothiazoleacetonitrile with chloroacetic acid anilides. An X-ray crystallographic study of 1-benzoyl-3,5-diphenyl-3H-pyrrolo[2′,3′:4,5]pyrimido[6, 1-b]benzothiazole-6-ium-2-olate was carried out to confirm the structure of title compounds unambiguously. The charge distribution in the obtained betaines was discussed.

Full text of DOI:10.1055/s-2002-35992

PAPER
2717
A Simple Synthesis of 1-Acyl-3-aryl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]ben-
zothiazol-6-ium-2-olates: Betainic Derivatives of a Novel Heterocyclic System
Synthesisof
a
N
l
ovel
H
i
etrocy
z
clic
S
yste
m
aveta V. Resnyanskaya,a Anton V. Tverdokhlebov,*a Yulian M. Volovenko,a Oleg V. Shishkin,b
Roman I. Zubatyukb
a
Kiev National Taras Shevchenko University, Volodimirska str., 62, 01033, Kiev, Ukraine
E-mail: atver@mail.univ.kiev.ua
b
Scientific Research Department of Alkali Halide Crystals, STC ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine,
60 Lenina ave., 310001, Khar’kov, Ukraine
Received 10 July 2002; revised 14 September 2002
in this field, we were interested in the preparation of hi-
Abstract: The title compounds were obtained by acylation of 5-
therto unknown derivatives with isomeric oxomethylene
moiety topology, namely 5-amino-2-pyrrolones 2 (X =
H2, Y = O) (Figure 1), and in the comparison of their prop-
amino-1-aryl-4-(2-benzothiazolyl)-2,3-dihydro-2-pyrrolones with
3-fold excess of acid chlorides. Starting pyrrolones were prepared
in high yields by alkylation of 2-benzothiazoleacetonitrile with
chloroacetic acid anilides. An X-ray crystallographic study of 1- erties with those of compounds 1. Since the above-men-
benzoyl-3,5-diphenyl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzo-
tioned conjugation cannot be realized in the structure 2,
thiazole-6-ium-2-olate was carried out to confirm the structure of ti-
the desired 2-pyrrolone derivatives are assumed to be
tle compounds unambiguously. The charge distribution in the
more reactive. Herein, the synthesis of compounds of type
obtained betaines was discussed.
2 as well as the results of the study of their acylation is re-
ported.
Key words: acylations, alkylations, 5-amino-2-pyrrolones, hetero-
cycles, pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazoles
The different methods for the preparation of various 4-
heteroaryl substituted 5-amino-3-pyrrolones have been
elaborated in our laboratory.1,2 In particular, the 5-amino-
4-(2-benzothiazolyl)-2,3-dihydro-3-pyrrolones 1 (X = O,
Figure 1 The structures of compounds 1: X = O, Y = H2; and 2:
X = H2, Y = O
Y = H2) (Figure 1) were synthesized.2d–f,2h Further inves-
tigation of their chemistry revealed a low reactivity of
both the amino and the carbonyl groups. Thus, aminopyr-
A literature search revealed a synthetic approach to the 5-
amino-2-pyrrolones via alkylation of malononitrile or eth-
rolones 1 were found not to give typical amine derivatives
under treatment with acid chlorides and isocyanates2h and
yl cyanoacetate with chloroacetic acid anilides,4 and was
not to form hydrazones at the carbonyl moiety.2f This be-
successfully applied to the synthesis of target derivatives.
havior was explained by strong vinylogous amide conju-
Thus, 5-amino-1-aryl-4-(2-benzothiazolyl)-2,3-dihydro-
2-pyrrolones 3 were obtained in high yields by alkylation
of benzothiazoleacetonitrile 4 with chloroacetic acid anil-
ides 5 in the presence of K2CO3 (Scheme 1). The possible
gation between amino and carbonyl groups of
aminopyrrolones 1. Recently the conjugation has been
confirmed by an X-ray crystallographic study, which es-
tablished the considerable deviations of the appropriate
alkylation of the nitrogen atom of the benzothiazole
bonds length in the -enaminoketone moiety from their
moiety5 was not observed. Moreover, this method turned
standard values.2h The same conjugation was noted for re-
out to be very convenient and the isolation procedure was
lated derivatives by other researchers,3 also on the basis of
simple, allowing it to be used for large scale preparation
crystallographic investigations. Continuing our research
Scheme 1 3, 5: Ar = a: Ph, b: 4-(i-Pr)C6H4, c: 1-naphthyl, d: 3-MeOC6H4, e) 5-Cl,2-MeOC6H3, f: 2,4-Me2C6H3, g: 2,4-F2C6H3, h: 4-EtOC6H4,
i) 4-NO2C6H4, j: 2-BrC6H4, k: 4-(t-Bu)C6H4
Synthesis 2002, No. 18, Print: 19 12 2002.
Art Id.1437-210X,E;2002,0,18,2717,2724,ftx,en;Z10102SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2718
E. V. Resnyanskaya et al.
PAPER
(ca. 0.5 mol) without modification. Since certain 5-amino- ton singlet. That allows us to state that magnetically non-
2-pyrrolone derivatives were reported to posses equivalence protons of the amino group in the 3-pyrrolo-
antimicrobial4d,f and radioprotective4e activities the com- nes 1 is caused by the amide-like restricted C–N bond ro-
pounds 3 can be also interesting from the biological view- tation.
point.
Further investigation was directed towards the study of
The structure of pyrrolones 3 was assigned on the basis of acylation of 5-amino-2-pyrrolones 3a,b with acid chlor-
analytical and spectral data. Their IR spectra revealed a ides. In contrast to their isomers 1, compounds 3a,b, were
strong absorption band at 1715–1735 cm–1, which is a typ- found to react readily with acid chlorides yielding the
ical value for carbonyl vibration of 5-membered lactams.6 products containing two acyl residues. The betainic struc-
Absorption of the primary amino group was also present ture of 1-acyl-3-aryl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-
at 3150–3330 cm–1, while there was no absorption of ni- b]benzothiazol-6-ium-2-olates 6 was assigned to them
trile. 1H NMR spectra of compounds 3 recorded in (Scheme 2). It can be represented as a superposition of the
DMSO-d6 solution exhibited a two-proton singlet of the four canonic structures A–D (Scheme 3) with positive
methylene group at 3.4 ppm and a set of signals from ben- charge distributed between nitrogen atoms at third and
zothiazole moiety (two doublets at 7.8 and 7.6, and two sixth positions and the negative one delocalized at the -
triplets at 7.3 and 7.1 ppm). The signal from amino group diketone moiety. Betaines 6 were the sole obtained prod-
protons was observed at 7.3–7.8 ppm region as a two pro- ucts when the reaction was performed in various molar ra-
ton D2O-exchangeable singlet. The protons of aryl group tio of the reagents. However, the highest yields of
exhibited their signals at expected values. Therefore, ac- compounds 6 ( 70%) were achieved using 3-fold excess
cording to the spectral data compounds 3 exist as amino- of the acid chloride. The additional equivalent of the acid
oxo tautomers at least in DMSO-d6 solution. It is notewor- chloride is supposed to act as a dehydrating agent for bis-
thy that the methylene group of the 1-naphthyl substituted acylated intermediates 7 (Scheme 2).
derivative 3c appears in its 1H NMR spectrum as two one-
The structure of compounds 6 was initially deduced from
proton doublets at 3.55 and 3.70 ppm with the coupling
the spectral data. First of all, the significant difference in
constant J = 21.5 Hz. It is explained in terms of hindered
the spectra of 5-methyl compounds 6c,e and 5-aryl deriv-
rotation of the naphthyl group around C–N bond due to
1
atives 6a,b,d,f–i should be mentioned. Thus, H NMR
substituents at second and fifth positions of the pyrroline
ring. Hence, the molecule of 3c acquires an axial chirality
spectra of compounds 6c,e showed 1 H doublet at 8.4–8.5
ppm and 3 H singlet at 3.2–3.3 ppm, which are in too low
and the methylene protons become diastereotopic, as a re-
field as for an ordinary aryl proton and C-methyl group re-
sult their signal transforms from a singlet into two dou-
spectively. These signals were assigned to the 7-H and 5-
blets with geminal spin-spin coupling.
CH3, the deshielding of these protons can be explained by
It should be noted that in contrast to compounds 3 the ami- the influence of ring current of pyrimidine nuclei at 7-H
no group signals of the 3-pyrrolones 1 was observed in 1H and of benzene moiety at 5-CH3. Moreover, a NOESY ex-
NMR spectra as two separate one-proton singlets in the periment carried out for compound 6c revealed the posi-
range of 8.0–9.0 ppm.2d–h It could be explained by either tive NOE between the above-mentioned signals, thus
intramolecular hydrogen bond between amino group pro- confirming pyrimidine ring closure. The signals of the
ton and the nitrogen of the neighboring benzothiazolyl other protons of the former benzothiazolyl moiety are
substituent or the restricted C–N bond rotation due to shifted downfield to 0.3–0.4 ppm pointing at some cation-
amide-like conjugation with the carbonyl. The fragment ic character of the nitrogen atom.
consisting of vicinal amino group and benzothiazole moi-
On the other hand, the 1H NMR spectra of 5-aryl deriva-
ety is retained in the structure of 2-pyrrolones 3, but the
tives 6a,b,d,f–i exhibited an opposite effect. An unusually
signal of the amino group protons is observed as two-pro-
high-field 1 H doublet at 6.4–6.7 ppm was observed there-
Scheme 2
Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of a Novel Hetrocyclic System
2719
Scheme 3
in. It also was assigned to the 7-H. Its strong shielding is charged derivatives of partially hydrogenated
caused by the ring current of 5-aryl group. The latter is ap- benzothiazolo[3,2-c]quinazoline system were described
proximately perpendicular to the tetracycle’s plane, there- previously.7 It is noteworthy that some pyrimido[6,1-
fore 7-H turned out to be located almost above the center b]benzothiazoles, which moiety is included into the skel-
of aryl substituent. At the same time the signals of the oth- eton of 6, were reported to exhibit antiallergic,8a,b anti-
er protons of the benzothiazolyl moiety remained shifted inflammatory8a,b and plant protective8c properties.
downfield as in 5-methyl derivatives 6c,e. The above giv-
en spectral data are similar to those reported for 5-methyl
About 15 years ago Elgemeie and co-workers9 described
the synthesis of 1-phenylpyrimido[6,1-b]benzothiazole-
3-thiones 9 (Figure 3) by treatment of 2-benzothiazole
acetic acid derivatives with benzoyl isothiocyanate. The
structure of 9 contains a moiety of phenyl substituted py-
rimido[6,1-b]benzothiazole similar to that found in 5-aryl
substituted derivatives 6a,b,d,f–i. Consequently, the
and 5-aryl derivatives of pyrrolo[2 ,3 :4,5]pyrimido[6,1-
a]benzimidazole system 8 (Figure 2).1c,2f The latter is a
good model for the system under investigation and the re-
semblance of their spectra confirms the assigned structure
6. Moreover, the 13C NMR spectra recorded for 5-methyl
and 5-aryl derivatives 6e and 6d together with COSY,
HSQC and HMBC experiments performed to facilitate the
high-field doublet described above for compounds
1
6a,b,d,f–i should be present in H NMR spectra of 9.
signals assignment, were in good agreement with the
However, there was nothing upfield from 7.2 ppm in the
structure 6. Finally, mass spectra of 6e and 6d established
spectra of compounds 9 reported.9 Moreover the signals
expected M.+ values 415 and 576, respectively.
separated from the other ones at high-field side were not
described in the spectra of derivatives 9. Hence a wrong
structure had been assigned anyway. Our assignment of
1
structure 6 seems to be clearer as only IR and H NMR
spectra were used by Elgemeie and co-workers to confirm
their structure. Nevertheless, to exclude any doubt and to
obtain the information about bond length, allowing to
consider the charges distribution in the betaines 6, the X-
ray crystallographic study of 1-benzoyl-3,5-diphenyl-3H-
pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazole 6a was
carried out. It proved the structure 6 to be true (Figure 4),
therefore Elgemeie’s structure 9 should be revised.
Figure 2 The structure of comound 8
To the best of our knowledge compounds 6 are the repre-
sentatives of a hitherto unknown heterocyclic system –
pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazole.
The
preparation of their analogues – benzothiazolo[3,2-
c]quinazoline derivatives, where pyrrole ring is replaced
by a benzene one, was reported starting from 2-(2-ami-
nophenyl)benzothiazole or -benzothiazoline.7 Certain
similarities of the approaches to the pyrimidine ring clo-
sure in both cases can be pointed out, though only un-
Figure 3 The structure of compound 9
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2720
E. V. Resnyanskaya et al.
PAPER
The crystals of 6a suitable for X-ray analysis were ob- proton doublet at 7.76 ppm from 2 ,6 -H of p-toluoyl moi-
tained as a 1:1 solvate with DMF molecule. The above ety, while for derivative 6e corresponding correlation with
given assumption about mutual arrangement of 7-H and 5- the three-proton singlet of methyl at 2.33 ppm was ob-
aryl substituent in compounds 6a,b,d,f–i deduced from served. These values of 13C NMR shifts indicate their car-
1
their H NMR spectra is confirmed by X-ray data. Thus, bonyl character, hence the negative charge should be
the phenyl substituent C(20)–C(25) is turned out from placed at the oxygen at second position. Therefore, ac-
pyrrolopyrimidine plane at an angle 66.2o. Such confor- cording to the spectral data in DMSO-d6 solution canonic
mation results in intramolecular CH– bonding with fol- structures A and C seem to be more preferable than B and
lowing parameters: C(5)–H(5)–X, H(5)–X distance is D in contrast to the solid state.
2.57 Å, C(5)–H(5)–X angle is 142o, where X represents
the center of the phenyl ring C(20)–C(25).
In summary, a convenient method for 5-amino-4-(2-ben-
zothiazolyl)-2,3-dihydro-2-pyrrolones 3 preparation has
been worked out. Their acylation with acid chlorides has
been shown to lead to the derivatives of a novel hetero-
cyclic system namely
1-acyl-3-aryl-3H-pyrrolo-
[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-ium-2-olates 6.
The charge distribution in betaines 6 in solid state and in
their solution in DMSO has been discussed. The compar-
ison of the reactivity of compounds 3 with those of iso-
meric 3-pyrrolones
1
confirmed the amide-type
conjugation in 1 to be the cause of their low reactivity.
2-Benzothiazoleacetonitrile (4) was prepared as reported.11 Chloro-
acetic acid anilides 5a–k were obtained according to described pro-
cedures.12 Acid chlorides were commercially available or prepared
from corresponding commercially available acids via standard
methods. All mps were determined in capillary tubes in a Thiele ap-
paratus and are uncorrected. IR spectra were obtained for KBr tab-
1
Figure 4 X-ray molecular structure of compound 6a with the atom
numbering used in the crystallographic analysis
lets on a Pye Unicam SP 3-300 apparatus. H NMR spectra were
recorded on a Varian VXR-300 (300 MHz) spectrometer in DMSO-
d6 solution. Chemical shifts ( ) are given in ppm downfield from in-
ternal standard (SiMe4). J values are in Hz. Besides the standard ab-
breviations, dist for distorted and Bth for benzothiazolyl were used.
13C NMR and 2D NMR experiments were performed on a Bruker
Analysis of the bonds length in the -diketone moiety al-
lows to suggest more contribution from canonic structures
B and D (Scheme 3) than of A and C in the molecule of
6a. So, the bond C(13)–O(1) [1.241(5) Å] is considerably
longer than C(12)–O(2) [1.218(5) Å] and the bond C(11)–
C(12) [1.446(6) Å] is also longer than C(11)–C(13)
[1.434(6) Å]. Therefore the negative charge is located pre-
dominantly at O(1). Probably, it is due to its additional
stabilization by donating interaction O(1) S(1) [the dis-
tance is 2.66 Å whereas van der Waals radii sum is 3.09
Å,10 the angle O(1)–S(1)–C(1) is 162.3o].
1
Avance 500 (500 MHz for H, 125 MHz for 13C) spectrometer.
Mass spectra were determined on a Varian 212 instrument at 70 eV.
The purity of all compounds prepared was checked by 1H NMR.
5-Amino-1-aryl-4-(2-benzothiazolyl)-2,3-dihydro-2-pyrrolones
3a–k; General Procedure
Powdered K2CO3 (0.485 g, 3.5 mmol) was added to a solution of 2-
benzothiazoleacetonitrile (4; 0.522 g, 3 mmol) and 2-chloroaceta-
nilide 5 (3 mmol) in absolute EtOH (4 mL) and the resulting mixture
was refluxed for 1 h. After cooling, the precipitate formed was fil-
tered, thoroughly washed with H2O and dried to yield pure com-
pounds 3a–k ( 60%). An additional portion (20–30%) can be
obtained by pouring the filtrate into H2O, filtration of the precipitat-
ed solid and recrystallization from appropriate solvent.
The positive charge in compound 6a is effectively delo-
calized at the chain N(1)–C(8)–N(2)–C(9)–N(3) and is
distributed between N(1) and N(3) approximately equally.
This is confirmed by the close values of N(1)–C(8) and
N(3)–C(9) bond lengths [1.371(5) Å and 1.366(5) Å, re-
spectively]. The bonds N(2)–C(8) and N(2)–C(9) are also
almost equal [1.327(5) Å and 1.330(5) Å, respectively].
So in the solid state, the molecule 6a is represented by su-
perposition of canonic structures B and D with insignifi-
cant contributions from A and C.
However, 13C NMR data allow us to suggest that the neg-
ative charge distribution in 6 in their solutions is different.
Thus, 13C NMR spectra of compounds 6d and 6e show the
presence of the lowest-field signal at 184.0 and 188.2 ppm
respectively, assigned to carbon of oxo group of the acyl
substituent at first position based on long-range C-H cor-
relation data. For 6d this signal gave correlation with two-
5-Amino-4-(2-benzothiazolyl)-2,3-dihydro-1-phenyl-2-pyrrol-
one (3a)
Mp 225 °C (1,4-dioxane); yield: 0.75 g (81%).
IR: 3420, 3050 (NH), 1720 (C=O), 1630, 1500, 1490, 1380, 1295,
1255, 740, 685 cm–1.
1H NMR: = 3.44 (s, 2 H, CH2), 7.11 (t, 1 H, J = 7.8 Hz, 5-HBth),
7.31 (t, 1 H, J = 7.8 Hz, 6-HBth), 7.35 (d, 2 H, J = 7.2 Hz, 2,6-HAr),
7.40 (br s, 2 H, NH2), 7.49 (t, 1 H, J = 7.8 Hz, 4-HAr), 7.56 (m, 2 H,
3,5-HAr), 7.63 (d, 1 H, J = 7.8 Hz, 7-HBth), 7.78 (d, 1 H, J = 7.8 Hz,
4-HBth).
13C NMR: = 32.62 (CH2), 77.06 (4-C), 118.95 (6-CBth), 120.72 (7-
CBth), 120.77 (4-CAr), 121.38 (5-CBth), 125.05 (3,5-CAr), 125.79 (4-
CBth), 129.63 (7a-CBth), 134.44 (2,6-CAr), 145.39 (1-CAr), 151.00
(3a-CBth), 153.54 (2-CBth), 164.16 (5-C), 174.11 (C=O).
Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of a Novel Hetrocyclic System
2721
Anal. Calcd for C17H13N3OS: C, 66.43; H, 4.26; N, 13.67; S, 10.43.
Found: C, 66.25; H, 4.31; N, 13.55; S, 10.42.
13C NMR: = 32.09 (CH2), 55.26 (OCH3), 76.47 (4-C), 112.97 (3-
CAr), 117.99 (4-CAr), 119.64 (6-CBth), 120.84 (7-CBth), 121.12 (5-
CBth), 123.77 (5-CAr), 124.71 (4-CBth), 129.41 (7a-CBth), 131.52 (6-
5-Amino-4-(2-benzothiazolyl)-2,3-dihydro-1-[4-(isopropyl)phe-
nyl]-2-pyrrolone (3b)
CAr), 134.29 (1-CAr), 150.24 (3a-CBth), 155.84 (2-CBth), 164.30 (5-
C), 164.32 (2-CAr), 172.99 (C=O).
Mp 231 °C (EtOH); yield: 0.94 g (90%).
Anal. Calcd for C18H14ClN3O2S: C, 58.14; H, 3.79; Cl, 9.53; N,
11.30; S, 8.62. Found C, 58.15; H, 3.71; Cl, 9.47; N, 11.25; S, 8.82.
IR: 3430, 3150 (NH), 2950 (CH), 1715 (C=O), 1620, 1485, 1280,
1195, 1150, 745 cm–1.
5-Amino-4-(2-benzothiazolyl)-1-(2,4-dimethylphenyl)-2,3-di-
hydro-2-pyrrolone (3f)
Mp 211 °C (1,4-dioxane); yield: 0.71 g (71%).
1H NMR: = 1.27 (d, 6 H, J = 6.9 Hz, 2 CH3), 2.98 [m, 1 H,
CH(CH3)2], 3.42 (s, 2 H, CH2), 7.10 (t, 1 H, J = 7.8 Hz, 5-HBth),
7.20–7.35 (m, 5 H, 6-HBth, 2 HAr, NH2), 7.40 (d, 2 HAr, J = 8.4 Hz),
7.62 (d, 1 H, J = 7.8 Hz, 7-HBth), 7.77 (d, 1 H, J = 7.8 Hz, 4-HBth).
13C NMR: = 23.28 (2 CH3), 32.83 (CH2), 34.68 (CHMe2), 76.99
(4-C), 118.81 (6-CBth), 120.84 (7-CBth), 121.40 (5-CBth), 125.48 (4-
1H NMR: = 2.13 (s, 3 H, CH3), 2.37 (s, 3 H, CH3), 3.44 (s, 2 H,
CH2), 7.05–7.18 (m, 3 H, 5-HBth, 5,6-HAr), 7.22 (s, 1 H, 3-HAr), 7.30
(m, 3 H, 6-HBth, NH2), 7.61 (d, 1 H, J = 7.8 Hz, 7-HBth), 7.78 (d, 1
H, J = 7.8 Hz, 4-HBth).
13C NMR: = 17.72 (CH3), 20.65 (CH3), 30.95 (CH2), 77.22 (4-C),
118.81 (6-CBth), 120.19 (7-CBth), 120.34 (5-CAr), 120.59 (5-CBth),
125.48 (4-CBth), 125.63 (4-CAr), 128.34 (7a-CBth), 128.80 (3-CAr),
130.50 (6-CAr), 134.81 (2-CAr), 144.68 (1-CAr), 150.86 (3a-CBth),
154.26 (2-CBth), 166.24 (5-C), 173.58 (C=O).
CBth), 127.05 (2,6-CAr), 127.30 (3,5-CAr), 129.68 (7a-CBth), 131.00
(4-CAr), 148.65 (1-CAr), 150.86 (3a-CBth), 154.10 (2-CBth), 164.17
(5-C), 173.02 (C=O).
Anal. Calcd for C20H19N3OS: C, 68.74; H, 5.48; N, 12.02; S, 9.18.
Found: C, 68.65; H, 5.31; N, 12.05; S, 9.22.
5-Amino-4-(2-benzothiazolyl)-2,3-dihydro-1-(1-naphthyl)-2-
pyrrolone (3c)
Anal. Calcd for C19H17N3OS: C, 68.04; H, 5.11; N, 12.53; S, 9.56.
Found: C, 68.15; H, 5.21; N, 12.45; S, 9.62.
Mp 240 °C (1,4-dioxane); yield: 0.97 g (91%).
5-Amino-4-(2-benzothiazolyl)-1-(2,4-difluorophenyl)-2,3-di-
hydro-2-pyrrolone (3g)
Mp 247 °C (1,4-dioxane); yield: 0.84 g (82%).
1H NMR: = 3.44 (s, 2 H, CH2), 7.11 (t, 1 H, J = 7.5 Hz, 5-HBth),
7.22 (m, 1 HAr), 7.31 (t, 1 H, J = 7.5 Hz, 6-HBth), 7.41 (m, 1 HAr),
7.45–7.60 (m, 3 H, NH2, 1 HAr), 7.65 (d, 1 H, J = 7.5 Hz, 7-HBth),
7.78 (d, 1 H, J = 7.5 Hz, 4-HBth).
IR: 3430, 3150 (NH), 2950 (CH), 1715 (C=O), 1630, 1490, 1195,
765 cm–1.
1H NMR: = 3.55 (d, 1 H, J = 21.5 Hz, 3-H), 3.69 (d, 1 H, J = 21.5
Hz, 3-H), 7.13 (t, 1 H, J = 7.8 Hz, 5-HBth), 7.3–7.4 (m, 3 H, 6-HBth
,
NH2), 7.5–7.7 (m, 6 H, 7-HBth and 5 HAr), 7.82 (d, 1 H, J = 7.8 Hz,
4-HBth), 8.1 (m, 2 HAr).
13C NMR: = 31.09 (CH2), 76.32 (4-C), 111.46 (4-CAr), 119.56 (6-
13C NMR: = 32.83 (CH2), 76.06 (4-C), 108.12 (t, JCF = 28.4 Hz,
3-CAr), 118.64 (6-CBth), 120.84 (7-CBth), 122.39 (5-CBth), 125.11 (4-
CBth), 120.00 (7-CBth), 120.16 (7-CAr), 121.23 (5-CAr), 121.48 (6-
CAr), 122.43 (5-CBth), 124.21 (4-CBth), 125.92 (3-CAr), 128.47 (8-
CAr), 128.56 (4a-CAr), 130.59 (7a-CBth), 134.48 (2-CAr), 138.08 (8a-
CAr), 142.66 (1-CAr), 150.15 (3a-CBth), 155.26 (2-CBth), 164.99 (5-
C), 173.55 (C=O).
C
J
Bth), 126.09 (dd, JCF = 28.0, JCF = 2.8 Hz, 5-CAr), 130.35 (dd,
CF = 28.0, JCF = 2.8 Hz, 1-CAr), 131.06 (7a-CBth), 145.73 (t,
JCF = 7.2 Hz, 6-CAr), 151.49 (3a-CBth), 151.66 (dd, JCF = 260.0,
CF = 7.2 Hz, 4-CAr), 154.10 (2-CBth), 158.53 (d, JCF = 2.4 Hz, 5-C),
170.66 (d, JCF = 2.4 Hz, C=O), 172.40 (dd, JCF = 260.0 Hz,
CF = 7.2, 2-CAr).
J
Anal. Calcd for C21H15N3OS: C, 70.57; H, 4.23; N, 11.76; S, 8.97.
Found: C, 70.55; H, 4.31; N, 11.65; S, 8.92.
J
Anal. Calcd for C17H11F2N3OS: C, 59.47; H, 3.23; N, 12.24; S, 9.34.
Found: C, 59.35; H, 3.21; N, 12.33; S, 9.27.
5-Amino-4-(2-benzothiazolyl)-2,3-dihydro-1-(3-methoxyphe-
nyl)-2-pyrrolone (3d)
Mp 250 °C (1,4-dioxane); yield: 0.77 g (76%).
5-Amino-4-(2-benzothiazolyl)-1-(4-ethoxyphenyl)-2,3-dihydro-
2-pyrrolone (3h)
Mp 210 °C (EtOH); yield: 0.88 g (84%).
1H NMR: = 1.39 (t, 3 H, J = 7.1 Hz, CH2CH3), 3.40 (s, 2 H, CH2),
4.07 (q, 2 H, J = 7.1 Hz, CH2CH3), 7.04 (d, 2 H, J = 8.7 Hz, 3,5-
HAr), 7.09 (t, 1 H, J = 7.8 Hz, 5-HBth), 7.23 (d, 2 H, J = 8.7 Hz, 2,6-
HAr), 7.27–7.35 (m, 3 H, 6-HBth, NH2), 7.63 (d, 1 H, J = 7.8 Hz, 7-
1H NMR: = 3.43 (s, 2 H, CH2), 3.81 (s, 3 H, OCH3), 6.91 (m, 2 H,
2,4-HAr), 7.03 (d, 1 H, J = 7.8 Hz, 6-HAr), 7.10 (t, 1 H, J = 7.8 Hz,
5-HBth), 7.30 (t, 1 H, J = 7.8 Hz, 6-HBth), 7.4–7.5 (m, 3 H, 5-HAr,
NH2), 7.63 (d, 1 H, J = 7.8 Hz, 7-HBth), 7.78 (1 H, d, J = 7.8 Hz, 4-
HBth).
13C NMR: = 33.16 (CH2), 56.90 (OCH3), 77.61 (4-C), 105.53 (4-
CAr), 117.71 (2-CAr), 118.16 (6-CBth), 120.33 (7-CBth), 120.87 (5-
HBth), 7.80 (d, 1 H, J = 7.8 Hz, 4-HBth).
C
C
Bth), 122.11 (6-CAr), 126.46 (4-CBth), 127.31 (5-CAr), 129.59 (7a-
Bth), 148.42 (1-CAr), 150.38 (3a-CBth), 154.75 (2-CBth), 157.79 (3-
13C NMR: = 14.69 (CH3), 32.56 (CH2), 63.63 (OCH2), 77.39 (4-
C), 110.99 (3,5-CAr), 118.81 (6-CBth), 119.86 (7-CBth), 121.58 (5-
CAr), 163.49 (5-C), 175.18 (C=O).
CBth), 125.13 (4-CBth), 128.04 (2,6-CAr), 128.22 (7a-CBth), 139.92
Anal. Calcd for C18H15N3O2S: C, 64.08; H, 4.48; N, 12.45; S, 9.50.
Found: C, 64.05; H, 4.32; N, 12.65; S, 9.62.
(1-CAr), 148.67 (4-CAr), 150.19 (3a-CBth), 153.94 (2-CBth), 166.19
(5-C), 172.67 (2-C=O).
Anal. Calcd for C19H17N3O2S: C, 64.94; H, 4.88; N, 11.96; S, 9.12.
Found: C, 64.85; H, 4.67; N, 12.03; S, 9.21.
5-Amino-4-(2-benzothiazolyl)-1-(5-chloro-2-methoxyphenyl)-
2,3-dihydro-2-pyrrolone (3e)
Mp 221 °C (1,4-dioxane); yield: 0.83 g (75%).
5-Amino-4-(2-benzothiazolyl)-2,3-dihydro-1-(4-nitrophenyl)-2-
pyrrolone (3i)
Mp 252 °C (1,4-dioxane); yield: 0.87 g (83%).
1H NMR: = 3.43 (s, 2 H, CH2), 3.82 (s, 3 H, OCH3), 7.11 (t, 1 H,
J = 7.5 Hz, 5-HBth), 7.23 (d, 1 H, J = 9.0 Hz, 3-HAr), 7.31 (t, 1 H,
J = 7.5 Hz, 6-HBth), 7.38 (d, 1 H, J = 1.5 Hz, 6-HAr), 7.42 (br s, 2 H,
IR: 3200, 3150 (NH), 1730 (C=O), 1635, 1490, 1330, 1155, 850,
765, 750 cm–1.
3
4
NH2), 7.52 (dd, 1 H, J = 9.0, J = 1.5 Hz, 4-HAr), 7.63 (d, 1 H,
J = 7.5 Hz, 7-HBth), 7.78 (d, 1 H, J = 7.5 Hz, 4-HBth).
Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York

2722
E. V. Resnyanskaya et al.
PAPER
1H NMR: = 3.49 (s, 2 H, CH2), 7.14 (t, 1 H, J = 7.8 Hz, 5-HBth),
7.33 (t, 1 H, J = 7.8 Hz, 6-HBth), 7.59 (br s, 2 H, NH2), 7.67 (m, 3 H,
7-HBth, 2,6-HAr), 7.80 (d, 1 H, J = 7.8 Hz, 4-HBth), 8.38 (d, 1 H,
J = 9.0 Hz, 3,5-HAr).
1-Benzoyl-3,5-diphenyl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]-
benzothiazol-6-ium-2-olate (6a)
Mp 275 °C (1,4-dioxane); yield: 58% (Method A); 63% (Method
B).
13C NMR: = 31.69 (CH2), 76.05 (4-C), 118.49 (6-CBth), 120.94 (7-
IR: 3025 (CH), 1675, 1570, 1550, 1515, 1490, 1445, 1405, 1225,
1175, 835, 745, 690 cm–1.
CBth), 121.40 (5-CBth), 123.19 (3,5-CAr), 126.33 (4-CBth), 128.42
(7a-CBth), 129.59 (2,6-CAr), 135.09 (4-CAr), 150.86 (3a-CBth),
154.72 (2-CBth), 154.99 (1-CAr), 164.09 (5-C), 175.21 (C=O).
1H NMR: = 6.60 (d, 1 H, J = 8.7 Hz, 7-H), 7.19 (t, 1 H, J = 8.7 Hz,
8-H), 7.35–7.73 [m, 14 H, 5-R1, 3-C6H5, 3,4,5-H (COR1), 9-H], 7.78
[d, 2 H, J = 7.2 Hz, 2,6-H (COR1)], 8.16 (d, 1 H, J = 9.0 Hz, 10-H).
Anal. Calcd for C17H14N4O3S: C, 57.62; H, 3.98; N, 15.81; S, 9.05.
Found: C, 57.85; H, 3.97; N, 15.73; S, 9.01.
13C NMR: = 98.87 (1-C), 112.66 [4-C (5-R1)], 113.29 (11b-C),
121.72 (7-C), 126.27 (9-C), 127.15 [4-C (C6H4R)], 129.37 (10a-C),
129.61 [2,6-C (C6H4R)], 130.51 (8-C), 131.02 [2,6-C (COR1)],
131.19 (6a-C), 131.64 [1-C (COR1)], 131.81 [3,5-C (COR1)],
132.39 [3,5-C (5-R1)], 132.41 [3,5-C (C6H4R)], 133.27 (10-C),
135.19 [2,6-C (5-R1)], 137.50 [4-C (COR1)], 145.87 (N3-C), 153.69
(2-C), 155.38 (11a-C), 158.80 (3a-C), 164.02 [1-C (5-R1)], 174.20
(5-C), 184.22 (1-C=O).
5-Amino-4-(2-benzothiazolyl)-1-(2-bromophenyl)-2,3-dihydro-
2-pyrrolone (3j)
Mp 207 °C (n-BuOH); yield: 1.00 g (87%).
IR: 3250, 3150 (NH), 1715 (C=O), 1625, 1500, 1470, 1435, 1280,
1200, 1150, 740, 705 cm–1.
1H NMR: = 3.47 (s, 2 H, CH2), 7.14 (t, 1 H, J = 7.5 Hz, 5-HBth),
7.30 (t, 1 H, J = 7.5 Hz, 6-HBth), 7.42 (br s, 2 H, NH2), 7.47 (m, 2 H,
6,4-HAr), 7.57 (t, 1 H, J = 7.2 Hz, 5-HAr), 7.63 (d, 1 H, J = 7.5 Hz,
7-HBth), 7.80 (m, 2 H, 3-HAr, 4-HBth).
Anal. Calcd for C31H19N3O2S: C, 74.83; H, 3.85; N, 8.44; S, 6.44:
Found C, 74.95; H, 4.00; N, 8.53; S, 6.37.
1-(4-Methylbenzoyl)-5-(4-methylphenyl)-3-phenyl-3H-pyr-
rolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-ium-2-olate (6b)
Mp >300 °C (1,4-dioxane); yield: 45% (Method A), 65% (Method
B).
13C NMR: = 33.24 (CH2), 76.28 (4-C), 117.43 (6-CBth), 120.18 (4-
CAr), 120.41 (7-CBth), 121.40 (5-CBth), 126.04 (4-CBth), 130.28 (7a-
CBth), 130.94 (5-CAr), 135.72 (2-CAr), 137.45 (3-CAr), 143.83 (6-
CAr), 145.61 (1-CAr), 150.86 (3a-CBth), 154.38 (2-CBth), 163.64 (5-
C), 173.19 (C=O).
IR: 1670, 1510, 1445, 1410, 1225, 840, 820, 755 cm–1.
Anal. Calcd for C17H12BrN3OS: C, 52.86; H, 3.13; Br, 20.69; N,
10.88; S, 8.30. Found: C, 52.85; H, 3.17; Br, 20.63; N, 10.73; S,
8.37.
1H NMR: = 2.39 (s, 3 H, CH3), 2.47 (s, 3 H, CH3), 6.71 (d, 1 H,
J = 8.7 Hz, 7-H), 7.16–7.24 [m, 3 H, 8-H, 3,5-H (5-R1)], 7.35–7.54
(m, 8 H, 3,5-H (COR1), 3-C6H5, 9-H), 7.59 [d, 2 H, J = 7.5 Hz, 2,6-
H (5-R1)], 7.71 [d, 2 H, J = 8.1, 2,6-H (COR1)], 8.16 (d, 1 H, J = 8.7,
10-H).
13C NMR: = 21.28 (CH3), 21.38 (CH3), 99.17 (1-C), 113.29 (11b-
C), 120.54 (4-C (5-R1)), 122.37 (7-C), 125.84 (9-C), 127.15 [4-C
(C6H4R)], 128.49 (10a-C), 129.61 [2,6-C (C6H4R)], 130.92 [2,6-C
(COR1)], 131.05 [3,5-C (5-R1)], 131.16 (8-C), 131.19 (6a-C),
131.59 [1-C (COR1)], 132.83 [2,6-C (5-R1)], 133.24 [3,5-C
(COR1)], 132.41 [3,5-C (C6H4R)], 133.44 (10-C), 150.21 [4-C
(COR1)], 152.67 (2-C), 155.73 (11a-C), 158.74 (3a-C), 164.78 [1-C
(5-R1)], 172.87 (N3-C), 174.44 (5-C), 182.81 (1-C=O).
5-Amino-4-(2-benzothiazolyl)-1-[4-(tert-butyl)phenyl]-2,3-di-
hydro-2-pyrrolone (3k)
Mp 258 °C (n-BuOH); yield: 0.85 g (78%).
1H NMR: = 1.35 (s, 9 H, t-C4H9), 3.42 (s, 2 H, CH2), 7.10 (t, 1 H,
J = 7.8 Hz, 5-HBth), 7.20–7.40 (m, 5 H, 6-HBth, 2,6-HAr, NH2), 7.55
(d, 2 H, J = 8.7 Hz, 3,5-HAr), 7.63 (d, 1 H, J = 7.8 Hz, 7-HBth), 7.78
(d, 1 H, J = 7.8 Hz, 4-HBth).
13C NMR: = 31.42 (CH3), 31.55 (CH2), 34.15 (CMe3), 76.28 (4-
C), 117.34 (6-CBth), 120.84 (7-CBth), 121.76 (5-CBth), 123.84 (3,5-
CAr), 125.18 (4-CBth), 127.40 (2,6-CAr), 129.02 (7a-CBth), 142.60 (4-
CAr), 145.78 (1-CAr), 149.73 (3a-CBth), 154.46 (2-CBth), 164.17 (5-
C), 172.73 (C=O).
Anal. Calcd for C33H23N3O2S: C, 75.41; H, 4.41; N, 7.99; S, 6.10.
Found: C, 75.35; H, 4.33; N, 8.03; S, 6.07.
1-(4-Methylbenzoyl)-5-(4-methylphenyl)-3-[4-(isopropyl)phe-
nyl]-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-ium-
2-olate (6d)
Anal. Calcd for C21H21N3OS: C, 69.39; H, 5.82; N, 11.56; S, 8.82.
Found: C, 69.35; H, 5.87; N, 11.73; S, 8.97.
Mp >300 °C (1,4-dioxane); yield 49% (Method A), 65% (Method
B).
1-Aroyl-3,5-diaryl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]ben-
zothiazol-6-ium-2-olates 6a,b,d,f–i; General Procedure
Method A: The appropriate acid chloride (10 mmol) was added to a
solution of aminopyrrolone 3a or 3b (3 mmol) and Et3N (1.24 mL,
9 mmol) in anhyd 1,4-dioxane (7 mL) and the resulting mixture was
heated on a water-bath for 2 h. On cooling, the solid containing tri-
ethylamine hydrochloride and the desired compound precipitated. It
was thoroughly washed with large amount of H2O to give 20–30%
of pure 6. 1,4-Dioxane mother liquor was evaporated in vacuo to
dryness and the residue was treated with H2O, collected by suction
and recrystallized from appropriate solvent to yield an additional
portion of 6.
IR: 2950, 1665, 1510, 1450, 1415, 1395, 1225, 1180, 1060, 1015,
1000, 925, 840, 825, 755 cm–1.
1H NMR: = 1.24 [d, 6 H, J = 6.9 Hz, CH(CH3)2], 2.37 (s, 3 H,
CH3), 2.46 (s, 3 H, CH3), 2.95 [m, 1 H, CH(CH3)2], 6.67 (d, 1 H,
J = 8.4 Hz, 7-H), 7.19 [d, 2 H, J = 7.8 Hz, 3,5-H (5-R1)], 7.24 (t, 1
H, J = 8.4 Hz, 8-H), 7.35 [d, 2 H, J = 7.8 Hz, 3,5-H (COR1)], 7.44
(dist s, 4 H, 3-C6H4R), 7.54 (t, 1 H, J = 8.4 Hz, 8-H), 7.62 [d, 2 H,
J = 7.8 Hz, 2,6-H (5-R1)], 7.74 [d, 2 H, J = 7.8 Hz, 2,6-H (COR1)],
8.15 (d, 1 H, J = 8.4 Hz, 10-H).
13C NMR: = 22.65 (CH3), 22.93 (CH3), 24.86 [CH(CH3)2], 36.70
[CH(CH3)2], 98.94 (1-C), 113.78 (11b-C), 120.54 [4-C (5-R1)],
122.19 (7-C), 125.84 (9-C), 129.50 [2,6-C (C6H4R)], 129.74 (10a-
C), 130.77 (8-C), 130.92 [2,6-C (COR1)], 131.05 [3,5-C (5-R1)],
131.19 (6a-C), 131.59 [1-C (COR1)], 132.83 [2,6-C (5-R1)], 133.09
(10-C), 133.24 [3,5-C (COR1)], 133.35 [3,5-C (C6H4R)], 137.90 [4-
C (C6H4R)], 148.80 (N3-C), 150.21 [4-C (COR1)], 153.57 (2-C),
Method B: The appropriate acid chloride (10 mmol) was added to a
solution of aminopyrrolone 3a or 3b (3 mmol) in anhyd pyridine (5
mL) and the resulting mixture was heated at 100 °C for 2 h. After
cooling the solvent was removed in vacuo and the residue was treat-
ed with H2O, filtered and recrystallized from appropriate solvent to
yield compounds 6.
Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of a Novel Hetrocyclic System
2723
156.15 (11a-C), 159.42 (3a-C), 164.70 [1-C (5-R1)], 174.44 (5-C),
183.96 (1-C=O).
MS: m/z = 576(M.+), 524, 450, 407, 379, 303, 277, 249, 186, 136,
117.71 [3,5-C (COR1)], 122.19 (7-C), 124.73 (9-C), 129.16 (10a-
C), 129.45 [1-C (COR1)]), 129.50 [2,6-C (C6H4R)], 131.29 (8-C),
131.89 (6a-C), 132.71 (10-C), 133.35 [3,5-C (C6H4R)], 134.60 [2,6-
C (COR1)], 137.90 [4-C (C6H4R)], 138.18 [2,6-C (5-R1)], 142.79
[4-C (5-R1)], 148.80 (N3-C), 153.44 (2-C), 156.15 (11a-C), 159.41
(3a-C), 160.24 [1-C (5-R1)], 170.15 [4-C (COR1)], 174.72 (5-C),
183.34 (1-C=O).
119, 91, 78, 44, 28.
1-(2-Chlorobenzoyl)-5-(2-chlorophenyl)-3-[4-(isopropyl)phe-
nyl]-3H-pyrrolo[2 ,3 :4,5] pyrimido[6,1-b]benzothiazol-6-ium-
2-olate (6f)
Anal. Calcd for C36H29N3O4S: C, 72.10; H, 4.87; N, 7.01; S, 5.35.
Found: C, 71.97; H, 4.91; N, 7.03; S, 5.31.
Mp >300 °C (EtOH); yield: 68% (Method B).
1H NMR: = 1.20 [d, 6 H, J = 6.9 Hz, CH(CH3)2], 2.91 [m, 1 H,
CH(CH3)2], 6.47 (d, 1 H, J = 9.0 Hz, 7-H), 7.30–7.45 [m, 9 H, 3,4,5-
H (5-R1), 3,5-H (C6H4R), 3,4,5-H (COR1), 8-H], 7.60–7.75 [m, 2 H,
6-H (5-R1), 9-H] 7.80 [d, 2 H, J = 3.3 Hz, 2,6-H (C6H4R)], 7.86 [d,
1 H, J = 6.6 Hz, 6-H (COR1)], 8.32 (d, 1 H, J = 8.1 Hz, 10-H).
13C NMR: = 23.03 (CH3), 33.70 (CHMe2), 98.43 (1-C), 109.95 [4-
C (5-R1)], 114.27 (11b-C), 119.47 [1-C (5-R1)], 122.35 (7-C),
125.34 (9-C), 128.76 (10a-C), 129.50 [2,6-C (C6H4R)], 129.99 [5-
C (5-R1)], 130.19 (8-C), 130.95 [1-C (COR1)], 131.84 (6a-C),
132.01 [6-C (COR1)], 132.07 [5-C (COR1)], 133.14 [3-C (5-R1)],
133.35 [3,5-C (C6H4R)], 133.82 [3-C (COR1)], 134.08 (10-C),
137.90 [4-C (C6H4R)], 138.47 [4-C (COR1)], 139.51 [2-C (5-R1)],
140.20 [2-C (COR1)], 141.09 [6-C (5-R1)], 148.80 (N3-C), 153.07
(2-C), 156.15 (11a-C), 159.57 (3a-C), 173.96 (5-C), 185.47 (1-
C=O).
1-[4-(tert-Butyl)benzoyl]-5-[4-(tert-butyl)phenyl]-3-[4-(isopro-
pyl)phenyl]-3H-pyrrolo[2 ,3 :4,5] pyrimido[6,1-b]benzothiazol-
6-ium-2-olate (6i)
Mp >300 °C (EtOH); yield: 75% (Method B).
1H NMR: = 1.27 [d, 6 H, J = 7.2 Hz, CH(CH3)2], 1.35 (s, 9 H, t-
C4H9), 1.39 [s, 9 H, t-C4H9), 2.96 [m, 1 H, CH(CH3)2], 6.62 (d, 1 H,
J = 8.7, 7-H), 7.17 (t, 1 H, J = 8.7, 8-H), 7.30–7.45 [m, 6 H, 5-R1,
3,5-H (COR1)], 7.54 (t, 1 H, J = 8.7 Hz, 9-H), 7.61 (dist s, 4 H,
C6H4R), 7.74 [d, 2 H, J = 8.1 Hz, 2,6-H (COR1)], 8.16 (d, 1 H,
J = 8.7 Hz, 10-H).
13C NMR:
= 23.05 [CH(CH3)2], 30.10 [C(CH3)3], 30.15
[C(CH3)3], 33.41 (CHMe2), 33.57 (CMe3), 34.20 (CMe3), 98.72 (1-
C), 113.78 (11b-C), 121.94 (7-C), 125.08 (9-C), 127.56 [3,5-C (5-
R1)], 129.05 [2,6-C (C6H4R], 129.41 [3,5-C (COR1)], 130.00 (10a-
C), 130.29 (8-C), 130.98 [2,6-C (COR1)], 131.10 [1-C (COR1)],
131.19 (6a-C), 132.46 (10-C), 132.58 [4-C (5-R1)], 132.89 [2,6-C
(5-R1)], 134.29 [3,5-C (C6H4R)], 138.18 [4-C (C6H4R)], 147.59
(N3-C), 153.82 (2-C), 157.19 (11a-C), 159.67 (3a-C), 163.28 [4-C
(COR1)], 164.20 [1-C (5-R1)], 173.51 (5-C), 184.22 (1-C=O).
Anal. Calcd for C34H23Cl2N3O2S: C, 67.11; H, 3.81; N, 6.90; S,
5.27. Found: C, 67.15; H, 3.66; N, 6.74; S, 5.31.
1-(2-Furoyl)-5-(2-furyl)-3-[4-(isopropyl)phenyl]-3H-pyrrolo-
[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-ium-2-olate (6g)
Mp >300 °C (1,4-dioxane); yield: 72% (Method B).
IR: 2950, 1660, 1505, 1455, 1410, 1230, 1010, 885, 750 cm–1.
Anal. Calcd for C42H41N3O2S: C, 77.39; H, 6.34; N, 6.45; S, 4.92.
Found: C, 77.47; H, 6.27; N, 6.33; S, 4.81.
1H NMR: = 1.28 [d, 6 H, J = 6.9 Hz, CH(CH3)2], 2.99 [m, 1 H,
CH(CH3)2], 6.37 (d, 1 H, J = 9.0 Hz, 7-H), 6.63 [dist s, 1 H, 5-H (5-
R1)], 6.88 [dist s, 1 H, 4-H (5-R1)], 7.19 (d, 1 H, J = 2.4 Hz, 3-H (5-
R1)], 7.40–7.55 (m, 5 H, 8-H, C6H4R), 7.63 (t, 1 H, J = 9.0 Hz, 9-
H), 7.86 [dist s, 1 H, 5-H (COR1)], 8.03 [dist s, 1 H, 4-H (COR1)],
8.15 [d, 1 H, J = 3.0 Hz, 3-H (COR1)], 8.21 (d, 1 H, J = 9.0 Hz, 10-
H).
1-Acetyl-3-aryl-5-methyl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-
b]benzothiazol-6-ium-2-olates 6c,e; General Procedure
A solution of aminopyrrolone 3a or 3b (5 mmol) in Ac2O (6 mL)
was refluxed for 3 h. After cooling, the precipitate formed was fil-
tered, washed with H2O and dried to give pure compounds 6c or 6e.
These derivatives also could be obtained using AcCl according to
the Methods A or B described above in approximately equal yields.
13C NMR: = 23.58 (CH3), 33.09 (CHMe2), 98.38 (1-C), 110.03 [4-
C (5-R1)], 111.36 [4-C (COR1)], 113.74 (11b-C), 114.28 [3-C (5-
R1)], 121.57 (7-C), 126.18 (9-C), 129.40 [2,6-C (C6H4R)], 129.74
(10a-C), 130.38 (8-C), 131.27 (6a-C), 131.31 [3-C (COR1)], 132.58
[3,5-C (C6H4R)], 132.83 (10-C), 137.90 [4-C (C6H4R)], 143.96 [2-
C (COR1)], 144.45 [5-C (COR1)], 148.24 [5-C (5-R1)], 151.43 (N3-
C), 154.19 (2-C), 156.74 (11a-C), 158.90 (3a-C), 159.21 (5-C),
160.47 [2-C (5-R1)], 183.28 (1-C=O).
1-Acetyl-5-methyl-3-phenyl-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-
b]benzothiazol-6-ium-2-olate (6c)
Mp >300 °C (DMF); yield: 71%.
1H NMR: = 2.36 (s, 3 H, COCH3), 3.10 (s, 3 H, 5-CH3), 7.40–7.80
(m, 7 H, C6H5, 8-H, 9-H), 8.16 (d, 1 H, J = 8.0 Hz, 10-H), 8.48 (d,
1 H, J = 8.0 Hz, 7-H).
13C NMR: = 25.37 (5-CH3), 27.16 (COCH3), 90.22 (1-C), 112.84
(11b-C), 119.33 (7-C), 121.58 (9-C), 124.62 [4-C (C6H4R)], 125.45
[2 ,6 -C (C6H4R)], 125.02 [3 ,5 -C (C6H4)], 125.80 (8-C), 127.39
(10-C), 127.15 (10a-C), 130.42 (6a-C), 138.46 (N3-C), 143.23 (2-
C), 146.05 (3a-C), 149.57 (5-C), 163.80 (11a-C), 189.61 (1-C=O).
Anal. Calcd for C30H21N3O4S: C, 69.35; H, 4.07; N, 8.09; S, 6.17.
Found: C, 69.26, H, 4.07; N, 8.09; S, 6.11.
1-(4-Methoxybenzoyl)-5-(4-methoxyphenyl)-3-[4-(isopropyl)-
phenyl]-3H-pyrrolo[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-
ium-2-olate (6h)
Anal. Calcd for C21H15N3O2S: C, 67.54; H, 4.05; N, 11.25; S, 8.59.
Found: C, 67.47; H, 4.07; N, 11.33; S, 8.61.
Mp 286 °C (EtOH); yield: 69% (Method B),
1H NMR: = 1.23 [d, 6 H, J = 6.9 Hz, CH(CH3)2], 2.95 [m, 1 H,
CH(CH3)2], 3.82 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 6.69 (d, 1 H,
J = 8.7 Hz, 7-H), 6.93 [d, 2 H, J = 9.0 Hz, 3,5-H (5-R1)], 7.17 [d, 2
H, J = 8.7 Hz, 3,5-H (COR1)], 7.28 (t, 1 H, J = 8.7 Hz, 8-H], 7.37
[d, 2 H, J = 8.4 Hz, 3,5-H (C6H4R)], 7.45 [d, 2 H, J = 8.4 Hz, 2,6-H
(C6H4R)], 7.55 (t, 1 H, J = 8.7 Hz, 9-H), 7.65 [d, 2 H, J = 9.0 Hz,
2,6-H (5-R1)], 7.85 [d, 2 H, J = 8.7 Hz, 2,6-H (COR1)], 8.18 (d, 1 H,
J = 8.7 Hz, 10-H).
1-Acetyl-5-methyl-3-[4-(isopropyl)phenyl]-3H-pyrrolo-
[2 ,3 :4,5]pyrimido[6,1-b]benzothiazol-6-ium-2-olate (6e)
Mp >300 °C (DMF); yield: 77%.
IR: 2950, 1660, 1550, 1510, 1470, 1440, 1245, 1190, 1020, 1000,
890, 795, 750 cm–1.
1H NMR: = 1.29 [d, 6 H, J = 6.9 Hz, CH(CH3)2], 2.32 (s, 3 H,
COCH3), 3.00 [m, 1 H, J = 6.9 Hz, CH(CH3)2], 3.20 (s, 3 H, 5-CH3),
7.42 (dist s, 4 HAr, i-PrC6H4), 7.50–7.70 (m, 2 H, 8-H, 9-H), 8.12 (d,
1 H, J = 8.1 Hz, 10-H), 8.44 (d, 1 H, J = 8.1 Hz, 7-H).
13C NMR: = 24.58 (CH3), 32.85 (CHMe2), 55.02 (OCH3), 55.22
(OCH3), 99.61 (1-C), 113.85 (11b-C), 117.30 [3,5-C (5-R1)],
Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York

2724
E. V. Resnyanskaya et al.
PAPER
13C NMR: = 22.65 [CH(CH3)2], 25.76 (5-CH3), 26.18 (COCH3),
32.01 [CH(CH3)2], 90.11 (1-C), 112.35 (11b-C), 118.59 (7-C),
122.30 (9-C), 125.33 [2 ,6 -C (C6H4R)], 125.67 (8-C), 125.99 [3 ,5 -
C (C6H4R)], 127.00 (10-C), 128.38 (10a-C), 130.14 (6a-C), 135.37
[4-C (C6H4R)], 141.38 (N3-C), 143.40 (2-C), 146.67 (3a-C), 148.90
(5-C), 163.35 (11a-C), 188.24 (1-C=O).
(2) (a) Babichev, F. S.; Volovenko, Yu. M. Khim. Geterotsikl.
Soedin. 1976, 1147; Chem. Abstr. 1976, 85, 177228.
(b) Babichev, F. S.; Volovenko, Yu. M. Ukr. Khim. Zh.
(Russ. Ed.) 1977, 43, 711; Chem. Abstr. 1977, 87, 184451.
(c) Volovenko, Yu. M.; Babichev, F. S. Khim. Geterotsikl.
Soedin. 1977, 557; Chem. Abstr. 1977, 87, 68254.
(d) Volovenko, Yu. M.; Shokol, T. V.; Merkulov, A. S.;
Babichev, F. S. Ukr. Khim. Zh. (Russ. Ed.) 1993, 59, 55;
Chem. Abstr. 1993, 119, 160185. (e) Tverdokhlebov, A. V.;
Volovenko, Yu. M.; Shokol, T. V. Chem. Heterocycl. Cmpd.
(Engl. Transl.) 1998, 34, 44. (f) Resnyanskaya, E. V.;
Shokol, T. V.; Volovenko, T. V.; Tverdokhlebov, A. V.
Chem. Heterocycl. Cmpd. (Engl. Transl.) 1999, 35, 1230.
(g) Volovenko, Yu. M.; Volovnenko, T. A.; Tverdokhlebov,
A. V.; Ryabokon, I. G. Russ. J. Org. Chem. 2001, 37, 1323.
(h) Volovenko, Yu. M.; Tverdokhlebov, A. V.; Gorulya, A.
P.; Shishkina, S. V.; Zubatyuk, R. I.; Shishkin, O. V. Eur. J.
Org. Chem. 2002, 663.
MS: m/z = 415(M.+), 400, 372, 357, 303, 186, 159, 104, 44.
X-Ray Crystal Structure Determination of Compound 6a
Single crystals were obtained from DMF. Intensity data were col-
lected with a Siemens P3/PC difractometer using 2 / scan,
2
max = 50o, MoK radiation. Crystal data: C31H19N3O2S C3H7NO,
Mr = 570.68, triclinic, a = 10.087(6), b = 12.437(6), c = 13.319(7)
Å, = 114.03(4)o, = 90.37(4)o, = 112.73(4)o, V = 1380(1) Å3,
T = 293 K, space group P1, Z = 2, (MoK ) = 0.162 mm–1. 4728
reflections were measured, 4449 were unique, Rint = 0.0117. The
structure was solved by direct method with the SHELX97 program
package.13 The positions of hydrogen atoms were located by Fourier
difference synthesis and refined by riding model with Uiso = nUeq
of non-hydrogen atom bonded with hydrogen atom given (n = 1.5
for hydrogen atoms of methyl groups and n = 1.2 for the rest of hy-
drogen). The structure was refined by full-matrix, least-squares
methods, using 4449 reflections (R1 = 0.0058 at 1766 reflections
with F>4 (F), S = 0.784) and anisotropic thermal parameters for all
non-hydrogen atoms. The final wR(F2) value was 0.120.
(3) Gola, A.; Samartzi, E.; Bardakos, V.; Petroliagi, M.;
Igglessi-Markopoulou, O.; Markopoulos, J.; Barkley, J. V. J.
Heterocycl. Chem. 2000, 37, 681.
(4) (a) Schäfer, H.; Gewald, K. Monatsh. Chem. 1989, 120,
315. (b) Berghot, M. A.; Hanna, M. A.; Girges, M. M.
Pharmazie 1992, 47, 340. (c) Ghorab, M. M.; Abdel-
Hamide, S. G.; El-Hakim, A. E. Indian J. Heterocycl. Chem.
1995, 5, 115. (d) Abdel-Hamide, S. G. J. Indian Chem. Soc.
1997, 74, 613. (e) Ghorab, M. M.; Nassar, O. M.; Heiba, H.
I.; Amin, N. E. Acta Pharm. (Zagreb) 1998, 48, 101; Chem.
Abstr. 1998, 129, 239599. (f) Ibrahim, M. K. Egypt. J.
Pharm. Sci. 1999, 39, 519; Chem. Abstr. 2000, 133, 237942.
(g) Abbady, M. A.; Abdel-Hafez, Sh. H. Phosphorus, Sulfur
Silicon Relat. Elem. 2000, 160, 121.
Acknowledgments
Authors wish to thank ‘Enamine Ltd.’ (Kiev, Ukraine) and perso-
nally Dr. A. A. Tolmachev for financial support of present investi-
gation and Prof. H. Neunhoeffer, K. Runzheimer and E. Blyumin
(Darmstadt Technical University, Germany) for carrying out 13C
and 2D NMR experiments.
(5) Bahner, C. T.; Pickens, D.; Bales, D. B. J. Am. Chem. Soc.
1948, 70, 1652.
(6) Nakanishi, K. Infra Red Absorbtion Spectroscopy; Holden-
Day: San Francisco, 1962.
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Synthesis 2002, No. 18, 2717–2724 ISSN 0039-7881 © Thieme Stuttgart · New York