Synthesis of new heterocyclic compounds using 2-(3,3-dimethyl-1H- pyrroloisoquinolin-2(3H)-ylidene)malonaldehydes

Article abstract of DOI:10.1002/jhet.1735

Isoquinolin-5-ylhydrazinium chloride 13 and 5-bromoisoquinolin-8- ylhydrazinium chloride 14 were converted via Fischer syntheses with 3-methylbutan-2-one into indolenines, 2,3,3-trimethyl-3H-pyrrolo[2,3-f] isoquinoline 15 and 5-bromo-2,3,3-trimethyl-3H-pyrrolo[3,2-h]isoquinoline 16, respectively. Exposure of the indolenines to the Vilsmeier reagent produced diformyl compounds 17 and 18, which reacted with arylhydrazines to give the corresponding pyrazoles 19a, 19b, 19c, 19d, 19e, 19f, 19g, 19h, 19i and 20a, 20b, 20c, 20d, 20e, 20f, 20g. Reaction of 17 with thiourea gave a pyrimidine-2(1H)-thione 23 or with hydroxylamine hydrochloride, an isoxazole 24.

Full text of DOI:10.1002/jhet.1735

706
Synthesis of New Heterocyclic Compounds Using 2-(3,3-dimethyl-
1H-pyrroloisoquinolin-2(3H)-ylidene)malonaldehydes
Vol 51
a
b
b
c
*
Arash Afghan, Laia Roohi, Mehdi M. Baradarani, and John A. Joule
aDepartment of Chemical Engineering, Urmia University of Technology, Urmia 57155-419, Iran
bDepartment of Chemistry, Faculty of Science, University of Urmia, Urmia 57153-165, Iran
cThe School of Chemistry, The University of Manchester, Manchester M13 9PL, UK
*
E-mail: a.afghan@che.uut.ac.ir
Received December 7, 2011
DOI 10.1002/jhet.1735
Published online 3 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
Isoquinolin-5-ylhydrazinium chloride 13 and 5-bromoisoquinolin-8-ylhydrazinium chloride 14 were
converted via Fischer syntheses with 3-methylbutan-2-one into indolenines, 2,3,3-trimethyl-3H-pyrrolo[2,3-f]
isoquinoline 15 and 5-bromo-2,3,3-trimethyl-3H-pyrrolo[3,2-h]isoquinoline 16, respectively. Exposure of
the indolenines to the Vilsmeier reagent produced diformyl compounds 17 and 18, which reacted with
arylhydrazines to give the corresponding pyrazoles 19a–i and 20a–g. Reaction of 17 with thiourea gave a
pyrimidine-2(1H)-thione 23 or with hydroxylamine hydrochloride, an isoxazole 24.
J. Heterocyclic Chem., 51, 706 (2014).
INTRODUCTION
polyfunctional compounds reacted well with hydrazine or
arylhydrazines to produce corresponding pyrazoles 9, with
migration of the exocyclic double bond back into the pyrrole
ring, thus restoring the indolenine structure from which the
sequence started [8–11] (Scheme 2).
For the mechanism of formation of the aminomethylene
malondialdehydes, we suggested that a small equilibrium
concentration of an enamine tautomer 11 is successively
C-substituted twice and thus, before hydrolysis during
work-up, species 12 is present (Scheme 3). We propose
that a comparable mechanism operates in the work
described in the following paragraphs.
The recognition of the power of the species produced
by the combination of phosphoryl chloride with the amide
of a secondary amine (N-methylformanilide and N,N-
dimethylformamide have been most often utilized) has its
origins in a paper in 1896 [1]. Later, work by Fischer,
Muller and Vilsmeier [2], and then by Vilsmeier and
Haack [3], and later by the groups of Arnold [4] and
Meth-Cohn [5] clarified the process and made it into a
widely used regimen for acylation, especially formylation
of reactive aromatic and hetero-aromatic compounds, and
indeed nonaromatic compounds [6].
In 1959, Fritz [7] reported the N-formylation of the 3,3-
disubstituted 3H-indole (indolenine) 1 giving 2 using the
Vilsmeier reagent from DMF and POCl3. Further reaction
of 2 with the Vilsmeier reagent and hydrolysis produced 4.
Formation of this product probably involves the intermediacy
of 3, from which the N-formyl group is hydrolytically
removed. The enamine 5 was directly C-formylated, produc-
ing 6 (Scheme 1).
We recently described the reaction of indolenines 7 and
some pyridoindolenines, with the Vilsmeier reagent formed
from N,N-dimethylformamide and phosphorus oxychloride
to produce aminomethylene malondialdehydes such as
8 [8–10]. Additionally, we showed that these intriguing
RESULTS AND DISCUSSION
Diazotisation of 5-aminoisoquinoline and 5-bromo-8-
aminoisoquinoline, then reduction of the diazonium salts with
tin(II) chloride, produced the corresponding hydrazinium
chlorides 13 and 14. Reaction of isoquinolin-5-ylhydrazinium
chloride 13 with isopropyl methyl ketone in a Fischer reaction
produced the indolenine 2,3,3-trimethyl-3H-pyrrolo[2,3-f]
isoquinoline 15 in good yield. Similarly, 5-bromoisoquinolin-
8-yl hydrazinium chloride 14 reacted with isopropyl methyl
ketone in hot acetic acid to give 5-bromo-2,3,3-trimethyl-3H-
pyrrolo[3,2-h]isoquinoline 16 (Scheme 4). The structures of
© 2013 HeteroCorporation

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2-(3,3-dimethyl-1H-pyrroloisoquinolin-2(3H)-ylidene)malonaldehydes
707
Scheme 1
Me
Me
Me
Me
Hydrolysis
Vilsmeier reagent
Vilsmeier reagent
CHO
CHO
N
H
N
N
CHO
N
CHO
Me
1
2
3
4
Me
Me
Me
Vilsmeier reagent
CHO
N
N
Me
Me
5
6
Scheme 2
Me
Me
Me
Me
Me
Me
Me
R
R
R
CHO
CHO
N
Vilsmeier reagent
ArNHNH2 / EtOH
NR
N
N
N
H
R=H, Cl
7
8
9
Scheme 3
Me
Me
Me
Me
Me
Me
Me
NMe2
NMe2
Vilsmeier reagent
N
N
N
H
H
10
11
12
Scheme 4
three-hydrogen singlet signals for the imine-methyl groups,
resonating at d 2.39 and 2.42 ppm, respectively. Each com-
pound had an AB system for the ortho-related isoquinoline-
3- and 4-protons, in addition to singlet signals for the
isoquinoline C-1-protons.
Me
N
NHNH2 .HCl
Me
O
AcOH, reflux Me
Me
Me
+
Me
N
N
Each of the pyridoindolenines 15,16 was now reacted with
the Vilsmeier reagent, and diformyl compounds 17,18 were
obtained in yields of 75% and 80%, respectively (Scheme 5).
The structures of the aminomethylene malondialdehydes rest
on the observation of two 1-hydrogen singlets at d 9.80 and
d 9.85 for 17, and d 9.83 and d 9.88 for 18 corresponding to
aldehyde protons. Absorptions at 3140 cmÀ1 and 3165 cmÀ1
for 17 and 18, respectively, were evidence for the presence
of N–H bonds, further confirmed by 1H NMR signals for the
N-hydrogens appearing at d 14.30 (17) and d 14.55 (18),
respectively. As in our previous work, the aminomethylene
malondialdehydes reacted efficiently with hydrazine and
various arylhydrazines at reflux conditions to give pyrazoles
19a–i and 20a–g, with migration of the exocyclic double
bond to reform the imine unit (Scheme 5). For pyrazoles
13
15
Br
Br
O
AcOH, reflux
Me
Me
Me
Me
Me
N
+
Me
N
N
NHNH2 .HCl
14
16
the two pyridoindolenines were evident from their NMR
data: there were six-hydrogen singlets for the geminal
methyl groups, at d 1.36 and 1.39 ppm for 15 and 16, and
Journal of Heterocyclic Chemistry
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708
A. Afghan, L. Roohi, M. M. Baradarani, and J. A. Joule
Vol 51
Scheme 5
R
N
N
CHO
OHC
Me
Me
Me
N
R
NH
N
Me
Me
Me
RNHNH2
DMF, POCl3, 75°C
75%
Me
N
N
EtOH, reflux
N
19a
19b
19c
19d
19e
19f
15
17
H
Ph
3-MeO-C6H4
4-MeO-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-Me-C6H4
19g
CHO
NH
CHO
OHC
Me
O
19h
N
N
1) ethanol / reflux
2) H3O
O
Me
+
Me
N
R1
N
NHNH2
R2
CHO
R1
H
R2
CH3
H
17
19i
H3CO
OCH3
R
N
N
CHO
OHC
Me
Me
Me
Me
N
NH
N
Me
Me
RNHNH2
EtOH, reflux
DMF, POCl3, 75°C
80%
N
N
N
Me
Br
R
Br
Br
16
20a
20b
20c
20d
20e
20f
18
H
Ph
4-MeO-C6H4
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-Me-C6H4
20g
19a–i, the protons of the newly formed five-membered
heterocyclic ring resonated in the range d 8.38–8.80 and
for the pyrazoles 20a–g in the range d 8.37–8.71.
The reaction of dialdehyde 17 with thiourea in presence
of HCl(aq.) for 2 days at room temperature produced
pyrimidine thione 23 (Scheme 7). The structure of thione
23 was evident from its NMR data, a two-hydrogen singlet
for the pyrimidine ring protons at d 9.86, further confirmed
by a 13C NMR signal at d 189.92 for the thione group.
Absorptions at 2736 cmÀ1 and 1194 cmÀ1 were evidence
for existence of two tautomers, one with an S–H (thiol)
and one having a C=S (thione) group.
Finally, the reaction of dialdehyde 17 with hydroxylamine
in ethanol at room temperature for 2 days led to isoxazole
derivative 24. Attempt to formation of a comparable isoxa-
zole from dialdehyde 18 under the same conditions pro-
duced 25 (or its geometrical isomer) (Scheme 8).
In some cases, the reaction of diformyl compounds
17,18 with arylhydrazines in ethanol at room temperature
produced sharp melting mono-arylhydrazones 21a–b and
22 in excellent yields, which converted into corresponding
pyrazoles at reflux conditions. It was not possible to ascertain
which carbonyl group had reacted (Scheme 6). The 1H NMR
spectra of compounds 21c, 21g and 22g confirmed the
presence of a single isomer (cis or trans) in each case
[one possibility is shown below in each case]; the N-hydrogen
protons resonated in the range d 7.54–7.74 and imine
C-hydrogens in the range d 12.90–16.02.
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2-(3,3-dimethyl-1H-pyrroloisoquinolin-2(3H)-ylidene)malonaldehydes
709
Scheme 6
Me
Me
Me
Me
Me
Me
Br
OHC
N
OHC
N
OHC
N
H3CO
N
N
N
H
H
H
Me
NH
NH
Me
NH
N
N
N
21c
21g
22g
Scheme 7
HS
S
N
NH
N
CHO
NH
N
OHC
N
N
HCl(aq.) / ethanol
r.t. / 2 days
+ thiourea
N
N
N
17
23
Scheme 8
O
N
CHO
NH
OHC
Me
N
Me
Me
ethanol / r.t.
2 days
Me
+ HONH2 .HCl
N
N
17
24
CHO
NH
CN
NH
OHC
Me
OHC
Me
ethanol / r.t.
2 days
N
N
Me
+ HONH2 .HCl
Me
Br
Br
25
18
The structure of the isoxazole ring in 24 rests on
the observation of two 1-hydrogen singlets at d 9.90 and
d 10.05. The structure of 25 was evident from its molecular
formula, a singlet at d 9.51 assigned to a CHO group
and the NH proton resonance at d 16.12. Absorptions at
3201 cmÀ1 and 1905 cmÀ1 were evidence for the presence
of NH and CN functionalities, respectively.
15,16. Their condensation with hydrazine and various aryl-
hydrazines afforded corresponding pyrazole derivatives.
Also, reaction of 17 with thiourea and hydroxylamine hydro-
chloride produced thiopyrimidone and isoxazole derivatives,
respectively. On the other hand, condensation of 18 with
hydroxylamine hydrochloride afforded 3-oxopropanenitrile
derivative 25.
EXPERIMENTAL
CONCLUSION
General. Melting points were recorded on an electrothermal IA
9200 apparatus and are uncorrected. 1H and 13C NMR spectra were
recorded on a Bruker Avance AQS 300MHz spectrometer
Diformyl Compounds 17,18 were synthesized in good
yields by Vilsmeier–Haack formylation of pyridoindolenines
Journal of Heterocyclic Chemistry
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A. Afghan, L. Roohi, M. M. Baradarani, and J. A. Joule
Vol 51
(Brucker, Karlsruhe, Germany), at 300MHz and 75MHz, respec-
tively. Chemical shifts d are in parts per million (ppm) measured
in CDCl3 and DMSO-d6 as solvents and relative to TMS as the
internal standard. Infrared spectra were recorded on a Thermonicolet-
Nexus 670 FTIR instrument (Thermonicolet, USA). Microanalyses
were performed on a Leco Analyzer 932 (Leco, USA).
General procedure for synthesis of (15) and (16). A mixture
of isoquinolinyl hydrazine hydrochloride (5 g, 31 mmol) and
isopropyl methyl ketone (6.52mL, 60mmol) was heated at reflux
in acetic acid (30mL) for 3 h and then cooled, diluted with water
(50 mL) and neutralized with solid Na2CO3; then the crude
product precipitated, was filtered off and washed with water, then
recrystallized from ethanol to give the pure compound.
hydrate (80% w/w, 0.18 g, 3.5 mmol), or aryl hydrazine
(0.7 mmol), in absolute ethanol (15 mL) was heated with stirring at
reflux for 3–5 h. After cooling and concentrating the solution, the
resulting crystals were collected by filtration and recrystallized
from EtOH to give the corresponding pyrazoles.
3,3-dimethyl-2-(1H-pyrazol-4-yl)-3H-pyrrolo[2,3-f]isoquinoline
(19a). Yield of 95%; mp 234.6–237.4 ꢀC; FTIR (KBr, cmÀ1) nmax
1
3110, 2967, 2927, 1652, 1633, 1582, 1670, 1163, 941, 718; H
NMR (CDCl3): d 1.56 (s, 6H), 7.63 (d, J= 8.4 Hz, 1H), 7.89 (d,
J =8.4 Hz, 1H), 8.42 (d, J= 6.0 Hz, 1H), 8.62 (d, J = 6.0 Hz, 1H),
8.38 (s, 2H, pyrazole), 11–14 (bs, NH); 13C NMR (CDCl3): d
24.1, 54.57, 116.06, 116.59, 120.57, 125.23, 129.03, 129.35,
133.50, 142.78, 147.03, 148.36, 152.36, 189.86; Anal. Calcd. for
C16H14N4: C, 73.26; H, 5.38; N, 21.36% found: C, 73.15; H, 5.31;
N, 21.29%.
2,3,3-Trimethyl-3H-pyrrolo-[2,3-f]isoquinoline (15). Yield
of 75%; mp 111–116 ꢀC; FTIR (KBr, cmÀ1) nmax 3000, 2966,
1
3,3-dimethyl-2-(1-phenyl-1H-pyrazol-4-yl)-3H-pyrrolo[2,3-f]
isoquinoline (19b). Yield of 82%; mp 181.5–182.5 ꢀC; FTIR
(KBr, cmÀ1) nmax 3049, 2965, 2926, 1631, 1599, 1577, 1560,
2924, 1628, 1579, 1668, 1283, 847, 709; H NMR (CDCl3): d
1.36 (s, 6H), 2.39 (s, 3H), 7.55 (d, J = 8.1 Hz, 1H), 7.83 (d,
J = 8.1 Hz, 1H), 8.28 (d, J = 5.4 Hz, 1H), 8.58 (d, J = 5.4 Hz,
1H), 9.26 (s, 1H); 13C NMR (CDCl3): d 14.61, 18.32, 54.00,
115.09, 119.77, 124.18, 127.81, 127.99, 141.98, 145.50,
146.79, 151.38, 188.45; Anal. Calcd. for C14H14N2: C, 79.97;
H, 6.71; N, 13.32% found: C, 79.85; H, 6.68; N, 13.24%.
5-Bromo-2,3,3-Trimethyl-3H-pyrrolo-[3,2-h]isoquinoline (16).
Yield of 80%; mp 82–84 ꢀC; FTIR (KBr, cmÀ1) nmax 3036, 2964,
1
1669, 1280, 951, 757; H NMR (CDCl3): d 1.63 (s, 6H), 7.39
(tt, J1 = 7.5 Hz, J2 = 1.2 Hz, 1H), 7.54 (t, J = 8.4 Hz, 2H), 7.66
(d, J = 8.1 Hz, 1H), 7.82 (d, J = 8.1 Hz, 2H), 8.40 (s, 1H,
pyrazole), 8.34 (d, J = 5.7 Hz, 1H), 8.64 (d, J = 5.7 Hz, 1H),
8.69 (s,1H, pyrazole), 9.34 (s, 1H); 13C NMR (CDCl3): d
24.077, 54.58, 113.59, 118.23, 119.58, 120.55, 120.96, 125.96,
127.14, 129.03, 129.47, 129.64, 139.54, 140.67, 143.90,
147.12, 148.44, 152.30, 189.24; Anal. Calcd. for C22H18N4: C,
78.08; H, 5.36; N, 16.56% found: C, 77.99; H, 5.32; N, 16.54%.
2-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[2,3-f]isoquinoline (19c). Yield of 84%; mp
185.5–186.5 ꢀC; FTIR (KBr, cmÀ1) nmax 3081, 2975, 2925, 1631,
1610, 1573, 1556, 1495, 1268, 938, 833; 1H NMR (CDCl3):
d 1.59 (s, 6H), 3.88 (s, 3H), 6.89 (d, J = 7.5 Hz, 1H), 7.32–7.41
(m,3H), 7.61 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 8.37
(s, 1H, pyrazole), 8.40 (bs, 1H),8.66 (s, 1H, pyrazole), 8.66
(s, 1H), 9.30 (s, 1H); 13C NMR (CDCl3): d 24.04, 54.54, 55.57,
105.49, 111.46, 113.23, 116.56, 118.16, 120.49, 125.34, 127.19,
129.34, 130.38, 140.60, 142.97, 147.01, 148.39, 152.38, 160.63,
189.15; Anal. Calcd. for C23H20N4O: C, 74.98; H, 5.47; N,
15.21% found: C, 75.01; H, 5.43; N, 15.18%.
2-(1-(4-methoxyphenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[2,3-f]isoquinoline (19d). Yield of 80%; mp
253.0–255.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3075, 2999, 2967, 1644,
1567, 1524, 1504, 1253, 950, 833; 1H NMR (CDCl3): d 1.70
(s, 6H), 3.90 (s, 3H), 7.06 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz,
2H), 7.97 (d, J = 8.1 Hz, 1H), 8.24 (d, J = 8.1 Hz, 1H), 8.39
(s, 1H, pyrazole) , 8.59 (d, J = 6.0 Hz, 1H),8.77 (s, 1H, pyrazole),
8.99(d, J = 6.0 Hz, 1H), 9.59 (s, 1H); 13C NMR (CDCl3): d 24.00,
55.39, 55.66, 114.81, 118.10, 118.37, 124.19, 127.35, 127.44,
128.32, 132.82, 140.64, 146.19, 159.30, 181.47; Anal. Calcd. for
C23H20N4O: C, 74.98; H, 5.47; N, 15.21% found: C, 74.89; H,
5.43; N, 15.20%.
1
2926, 2865, 1618, 1608, 1582, 1649, 809; H NMR (CDCl3): d
1.39 (s, 6H), 2.42 (s, 3H), 6.68 (s, 1H), 8.03 (d, J= 6.0 Hz, 1H),
8.66 (d, J= 6.0 Hz, 1H), 9.98 (s, 1H); 13C NMR (CDCl3): d 15.69,
19.39, 55.15, 118.15, 119.59, 124.42, 127.72, 128.01, 133.12,
143.47, 143.76, 149.16, 190.84; Anal. Calcd. for C14H16BrN2: C,
58.15; H, 4.53; N, 9.69% found: C, 58.09; H, 4.41; N, 9.62%.
General procedure for synthesis of (17) and (18). To N,N-
dimethylformamide (16.8 mL, 180 mmol) cooled in an ice bath
was added dropwise phosphorus oxychloride (5.48 mL,
60 mmol) with stirring at below 5 ꢀC. After this addition,
indolenine (20 mmol) was added slowly. The cooling bath was
removed, and the reaction mixture was stirred at 75 ꢀC for 6 h.
The resulting solution was added to ice-cooled water and made
alkaline with NaOH (aq.) solution (pH = 8–9). The resulting
precipitate was collected by filtration, dried in air and
recrystallized from ethanol to give pure malondialdehyde.
2-(3,3-dimethyl-1H-pyrrolo[2,3-f]-isoquinolin-2(3H)-ylidene)
malonaldehyde (17). Yield of 85%; mp 188–190 ꢀC; FTIR (KBr,
cmÀ1) nmax 3140, 3055, 2964, 2868, 1682, 1660, 1647, 1514,
1164, 831, 769; 1H NMR (CDCl3): d 1.86 (s, 6H), 7.62 (d,
J=8.4 Hz, 1H), 7.78 (d, J=6.0 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H),
8.67 (d, J=6.0 Hz, 1H), 9.34(s,1H), 9.80 (s, CHO), 9.85 (s, CHO),
14.30 (bs, NH); 13C NMR (CDCl3): d 19.53, 52.71, 110.14,
116.82, 120.92, 119.91, 125.91, 128.40, 133.73, 141.30, 144.07,
153.09, 189.79, 187.67, 192.72; Anal. Calcd. for C16H14N2O2: C,
72.16; H, 5.30; N, 10.52% found: C, 72.09; H, 5.33; N, 10.49%.
2-(5-bromo-3,3-dimethyl-1H-pyrrolo[3,2-H]isoquinolin-2(3H)-
ylidene)malonaldehyde (18). Yield of 87%; mp 180–182 ꢀC; FTIR
(KBr, cmÀ1) nmax 2966, 2869, 2767, 1681, 1661, 1606, 1511, 1271,
1079, 1034, 886; 1H NMR (CDCl3): d 1.86 (s, 6H), 7.78 (s, 1H), 8.09
(d, J=6.0 Hz, 1H), 8.75 (d, J=6.0 Hz, 1H), 9.49 (s, 1H), 9.83
(s, CHO), 9.88 (s, CHO), 14.55 (bs, NH); 13C NMR (CDCl3): d
19.68, 52.39, 110.37, 118.70, 124.40, 127.97, 128.28, 133.25,
138.30, 144.87, 145.15, 146.31,189.83, 187.57, 192.81; Anal.
Calcd. for C16H13BrN2O2: C, 55.67; H, 3.80; N, 8.12% found: C,
55.65; H, 3.79; N, 8.09%.
2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[2,3-f]isoquinoline (19e).
Yield of 80%; mp
239.2–241.2 ꢀC; FTIR (KBr, cmÀ1) nmax 3049, 2972, 2931, 1645,
1486, 1676, 768; 1H NMR (CDCl3): d 1.70 (s, 6H), 7.39
(d, J=7.5 Hz, 1H), 7.49 (t, J=8.1 Hz, 1H), 7.73 (d, J=8.1 Hz,
1H), 7.88 (s, 1H), 7.99 (d, J= 8.1 Hz,1H), 8.30(d, J= 8.1 Hz,1H),
8.43 (s, 1H),8.60(d, J= 6 Hz, 1H), 8.80 (s, 1H), 8.99
(d, J= 6 Hz,1H), 9.67 (bs, 1H); 13C NMR (CDCl3): d 23.83, 55.55,
118.58, 120.00, 118.32, 124.48, 127.86, 160.81, 161.39, 165.63,
140.16, 141.27, 146.28, 181.15; Anal. Calcd. for C22H17ClN4:
C, 70.87; H, 4.60; N, 15.03% found: C, 70.81; H, 4.59; N, 15.01%.
General procedure for synthesis of (19a–i) and (21a–g). A
mixture of the diformyl compound 17/18 (0.7 mmol) and hydrazine
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938, 756; 1H NMR (CDCl3): d 1.63 (s, 6H), 7.40 (t, J= 7.5 Hz, 1H),
7.54 (t, J= 7.8 Hz, 2H), 7.81(s, 1H), 7.83(t, J = 8.4 Hz, 2H), 8.04(d,
J= 6.0 Hz, 1H), 8.40 (s, 1H, pyrazole), 8.70 (d, J =6.0 Hz, 1H),
8.71 (s, 1H, pyrazole), 10.08 (s, 1H); 13C NMR (CDCl3): d 24.14,
54.50, 118.049, 118.03, 119.63, 119.25, 123.99, 127.42, 127.55,
129.66, 133.26, 139.46, 140.68, 143.94, 149.18, 149.48, 180.27;
Anal. Calcd. for C22H17BrN4: C, 63.32; H, 4.11; N, 13.43% found:
C, 63.19; H, 4.03; N, 13.29%.
5-bromo-2-(1-(4-methoxyphenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[3,2-h]isoquinoline (20c). Yield of 85%; mp
198.0–199.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3108, 2998, 1625,
1582, 1524, 1503, 1648, 1267, 1253, 1183, 826; 1H NMR
(CDCl3): d 1.63 (s, 6H), 3.89 (s, 3H), 7.04 (d, J = 9.0 Hz, 2H),
7.72 (d, J = 9.0 Hz, 2H), 7.81 (s, 1H), 8.05 (d, J = 6 Hz,1H), 8.35
(s, 1H, pyrazole), 8.63 (s, 1H, pyrazole), 8.69(d, J = 6 Hz,1H),
10.08 (s, 1H); 13C NMR (CDCl3): d 24.18, 54.50, 55.62, 114.72,
117.19, 117.66, 121.27, 122.19, 124.17, 127.40, 127.51, 133.11,
133.29, 140.30, 143.51, 144.07, 149.30, 159.04, 180.53; Anal.
Calcd. for C23H19BrN4O: C, 61.75; H, 4.28; N, 12.52% found:
C, 61.71; H, 4.19; N, 12.49%.
2-(1-(4-chlorophenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-3H-pyrrolo
[2,3-f]isoquinoline (19f). Yield of 75%; mp 252.5–253.5 ꢀC; FTIR
(KBr, cmÀ1) nmax 3038, 2961, 2867, 1644, 1602, 1574, 1555, 1497,
1675, 952, 823; 1H NMR (CDCl3): d 1.70 (s, 6H), 7.53 (d,
J=9.0 Hz, 2H), 7.79 (d, J=9.0 Hz, 2H), 7.91 (d, J=8.4 Hz, 1H),
8.23 (d, J=8.4 Hz, 1H), 8.24 (s, 1H, pyrazole), 8.59 (d, J=6.0 Hz,
1H),8.80 (s, 1H, pyrazole), 8.97(d, J=6.0 Hz, 1H), 9.57 (s, 1H); 13C
NMR (DMSO-d6): d 23.23, 55.69, 117.76, 120.26, 121.20, 124.89,
127.73, 128.25, 129.10, 129.98, 130.58, 131.85, 132.14, 133.50,
138.33, 141.98, 148.32, 153.35, 181.39; Anal. Calcd. for C22H17ClN4:
C, 70.87; H, 4.60; N, 15.03% found: C, 70.69; H, 4.49; N, 14.98%.
2-(1-(4-methylphenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-3H-pyrrolo
[2,3-f]isoquinoline (19g). Yield of 86%; mp 191.0–192.0 ꢀC; FTIR
(KBr, cmÀ1) nmax 3040, 2968, 1630, 1577, 1561, 1520, 953, 941,
1
843, 819; H NMR (CDCl3): d 1.62 (s, 6H), 2.43 (s, 3H), 7.32
(d, J=8.4 Hz, 2H), 7.64 (d, J=8.1 Hz, 1H), 7.69 (d, J=8.4 Hz,
2H), 7.89 (d, J=8.1 Hz, 1H), 8.38 (s,1H, pyrazole), 8.41
(d, J=5.7 Hz, 1H), 8.64 (d, J=5.7 Hz, 1H), 8.65 (s, 1H, pyrazole),
9.32 (s, 1H); 13C NMR (CDCl3): d 18.02, 24.12, 54.53, 116.40,
118.03, 119.50, 120.44, 125.23, 127.05, 129.06, 129.35, 130.14,
137.30, 137.40, 140.42, 143.18, 146.91, 148.47, 152.52, 189.27;
Anal. Calcd. for C23H20N4: C, 78.38; H, 5.72; N, 15.90% found: C,
78.31; H, 5.69; N, 15.84%.
5-bromo-2-(1-(2-chlorophenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[3,2-h]isoquinoline (20d). Yield of 76%; mp
184.0–185.0 ꢀC; FTIR (KBr, cmÀ1) nmax 2966, 2926, 1625, 1587,
1
1488, 1649, 1275, 750; H NMR (CDCl3): d 1.63 (s, 6H), 7.43
2-(4-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)-1H-
pyrazol-1-yl)-8-methylquinoline-3-carbaldehyde (19h). Yield of
78%; mp 266.0–268.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3046, 2964,
(td, J1 = 7.5 Hz, J2 = 2.1 Hz, 1H), 7.47 (td, J1 = 7.5 Hz, J2 = 2.1 Hz,
1H), 7.60 (dd, J1 = 7.5 Hz, J2 = 2.1 Hz, 1H), 7.70 (dd, J1 = 7.5 Hz ,
J2 = 2.1 Hz, 1H), 7.83 (s, 1H), 8.07 (d, J = 6 Hz, 1H), 8.47 (s, 1H,
pyrazole), 8.63 (s, 1H, pyrazole), 8.68 (d, J = 6.0 Hz, 1H), 10.08
(s,1H); 13C NMR (CDCl3): d 24.15, 54.59, 118.20, 118.38,
119.19, 124.41, 127.53, 127.70, 127.93, 128.34, 129.84, 130.86,
132.02, 133.36, 137.47, 140.77, 143.03, 144.25, 149.11, 149.42,
180.38.; Anal. Calcd. for C22H16BrClN4: C, 58.49; H, 3.57; N,
12.40% found: C, 58.31; H, 3.51; N, 12.34%.
1
2924, 1697, 1631, 1616, 1591, 1492, 1433, 955, 759; H NMR
(CDCl3): d 1.68 (s, 6H), 2.85 (s,3H), 7.51 (t, J = 8.1 Hz, 1H), 7.66
(d, J = 8.1 Hz, 1H), 7.71 (s, 1H), 7.80 (s,1H), 7.89 (d, J = 8.1 Hz,
1H), 8.41 (d, J = 5.7 Hz, 1H), 8.55 (s, 1H, pyrazole), 8.63 (d,
J = 5.7 Hz, 1H), 8.75 (s, 1H, pyrazole), 9.29 (s, 1H), 9.37 (s, 1H),
10.80 (s, 1H, CHO); 13C NMR (CDCl3): d 18.75, 24.14, 54.69,
116.44, 118.30, 120.46, 122.79, 125.69, 126.51,127.22, 127.34,
128.69, 129.00, 129.42, 133.14, 136.72, 141.23, 142.63, 143.18,
146.66, 146.91, 147.15, 148.26, 152.45, 188.68, 190.11; Anal.
Calcd. for C27H21N5O: C, 75.16; H, 4.91; N, 16.23% found: C,
75.03; H, 4.83; N, 16.19%.
5-bromo-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo-[3,2-h]isoquinoline (20e). Yield of 80%; mp
240.0–241.0 ꢀC; FTIR (KBr, cmÀ1) nmax 2969, 2930, 1625, 1593,
1
1495, 1648, 1276, 947, 827; H NMR (CDCl3): d 1.63 (s, 6H),
7.36 (ddd, J1 = 8.1 Hz, J2 = 2.1 Hz, J3 = 0.9 Hz, 1H), 7.46
(t, J = 8.1 Hz, 1H), 7.72 (ddd, J1 = 8.1 Hz, J2 = 2.1 Hz, J3 = 0.9 Hz,
1H), 7.83 (s, 1H), 7.87 (t, J = 1.8 Hz, 1H), 8.06 (dd, J1 = 6 Hz,
J2 = 0.6 Hz, 1H), 8.39(s,1H, pyrazole), 8.68(s, 1H), 8.69
(d, J = 6.0 Hz, 1H), 10.07 (d, J = 0.6 Hz, 1H); 13C NMR (CDCl3):
d 24.07, 54.56, 117.24, 117.43, 118.41, 119.88, 119.19, 124.18,
127.34, 127.52, 130.70, 133.34, 135.55, 140.33, 141.04, 143.51,
144.12,149.18, 149.23, 180.03; Anal. Calcd. for C22H16BrClN4:
C, 58.49; H, 3.57; N, 12.40% found: C, 58.43; H, 3.55; N, 12.31%.
5-bromo-2-(1-(4-chlorophenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[3,2-h]isoquinoline (20f). Yield of 80%; mp
247.5–248.0 ꢀC; FTIR (KBr, cmÀ1) nmax 2969, 2930, 1625, 1593,
2-(4-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)-1H-
pyrazol-1-yl)-7-methoxyquinoline-3-carbaldehyde (19i). Yield of
80%; mp 236.0–238.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3046, 2964,
1
2924, 1697, 1631, 1616, 1591, 1492, 1433, 955, 759; HNMR
(CDCl3): d 1.55 (s, 6H), 3.91 (s, 3H), 7.13 (s, 1H), 7.29(s, 1H),
7.53(d, J = 7.8 Hz, 1H), 7.73–7.80(m, 2H), 8.30 (s, 1H), 8.46
(s,1H), 8.52 (s, 1H), 8.63 (s, 1H), 9.19 (m,2H),10.65(s, 1H,
CHO); 13CNMR (CDCl3): d 24.07,54.67,55.84,106.67, 116.48,
118.32, 120.43, 120.99, 121.06, 121.87, 125.64, 128.81, 129.51,
130.53, 140.39, 142.87, 143.25, 147.16, 148.38, 148.92,
150.19,163.85, 170.79, 173.10, 188.67, 189.98; Anal. Calcd. for
C27H21N5O2: C, 72.47; H, 4.73; N, 15.65% found: C, 72.41; H,
4.69; N, 15.61%.
1
1495, 1648, 1276, 947, 827; H NMR (CDCl3): d 1.63 (s, 6H),
7.61 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 7.82(s, 1H),
8.06 (d, J = 6 Hz, 1H), 8.38 (s, 1H, pyrazole), 8.69(s, 1H,
pyrazole), 8.70 (d, J = 6.0 Hz, 1H), 10.07 (s, 1H); 13C NMR
(CDCl3): d 24.07, 54.55, 117.26, 118.32, 120.72, 122.20, 124.20,
127.32, 127.70, 129.78, 133.18, 133.34, 137.96, 140.86, 143.46,
144.12, 149.20, 180.14; Anal. Calcd. for C22H16BrClN4: C,
58.49; H, 3.57; N, 12.40% found: C, 58.41; H, 3.52; N, 12.29%.
5-bromo-2-(1-(4-methylphenyl)-1H-pyrazol-4-yl)-3,3-dimethyl-
3H-pyrrolo[3,2-h]isoquinoline (20g). Yield of 80%; mp
198.0–199.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3035, 2968, 2920, 1625,
1580, 1519, 1425, 1647, 1275, 1188, 951; 1H NMR (CDCl3):
d 1.63 (s, 6H), 2.43 (s, 3H), 7.33 (d, J = 8.1 Hz, 2H), 7.70
5-bromo-3,3-dimethyl-2-(1H-pyrazol-4-yl)-3H-pyrrolo[3,2-h]
isoquinoline (20a). Yield of 92%; mp 245–246 ꢀC; FTIR (KBr,
1
cmÀ1) nmax 3185, 2970, 1623, 1586, 1649, 1276, 938, 812; H
NMR (DMSO-d6): d 1.53 (s, 6H), 7.96(dd, J1 =6.0Hz, J2 =0.6Hz,
1H), 8.23 (s, 1H), 8.50 (s, 2H, pyrazole), 8.64 (d, J= 6.0 Hz, 1H),
9.86 (d, J =0.6 Hz, 1H); 13C NMR (DMSO-d6): d 23.81, 54.78,
115.06, 116.98, 121.75, 125.61, 125.77, 132.62, 144.31, 145.19,
149.08, 149.20, 182.48; Anal. Calcd. for C16H13BrN4: C, 56.32;H,
3.84;N, 16.42% found: C, 56.18; H, 3.79; N, 16.31%.
5-bromo-3,3-dimethyl-2-(1-phenyl-1H-pyrazol-4-yl)-3H-pyrrolo
[3,2-h]isoquinoline (20b). Yield of 78%; mp 298.5–300.5 ꢀC; FTIR
(KBr, cmÀ1) nmax 3055, 2964, 1624, 1601, 1579, 1566, 1419, 1646,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

712
A. Afghan, L. Roohi, M. M. Baradarani, and J. A. Joule
Vol 51
(d, J = 8.1 Hz, 2H), 7.80 (s, 1H), 8.03 (d, J = 6 Hz,1H), 8.37 (s, 1H,
pyrazole), 8.67 (s, 1H, pyrazole), 8.69 (d, J = 6.0 Hz, 1H), 10.07(d,
J = 0.6 Hz, 1H); 13C NMR (CDCl3): d 18.01, 24.18, 54.48, 117.04,
117.79, 119.55, 122.23, 123.99, 127.37, 127.44, 130.16, 133.24,
137.19, 137.54, 140.44, 143.98, 149.19, 149.48, 180.38; Anal.
Calcd. for C23H19BrN4: C, 64.05; H, 4.44; Br, 18.53; N, 12.99%
found: C, 63.97; H, 4.34; N, 13.02%.
(DMSO-d6): d 1.19 (s, 6H), 8.19 (d, J = 8.1 Hz, 1H), 8.37(d,
J = 8.1 Hz, 1H ), 8.62 (d, J = 6.2 Hz, 1H), 8.69 (d, J = 6.2 Hz,
1H), 9.82 (s, 1H), 9.86 (s, 2H), 13.73 (bs, NH); 13C NMR
(DMSO-d6): d 19.92, 56.57, 110.45, 119.31, 119.10, 124.42,
124.51, 124.91, 127.59, 128.32, 128.58, 134.95, 134.98,
145.90,149.45, 152.90, 188.70, 189.92(C= S); Anal. Calcd. for
C17H14N4S: C, 66.64; H, 4.61; N, 18.29; S, 10.47% found: C,
66.59; H, 4.54; N, 18.18; S, 10.43%.
General procedure for synthesis of (21c, 21g and 22).
A
General procedure for synthesis of (24 and 25).
A
mixture of the diformyl compound 16 or 17 (0.57 mmol) and
aryl hydrazine (0.57 mmol) in absolute ethanol (15 mL) was
stirred at RT overnight. After cooling and concentrating the
solution, the resulting crystals were collected by filtration, air
dried and washed with cold EtOH.
2-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)-2-(2-(3-
methoxyphenyl) hydrazono)acetaldehyde (21c). Yield of 70%;
mp 151.5–152.5 ꢀC; FTIR (KBr, cmÀ1) nmax 3283, 3957, 2959,
2831, 1630, 1578, 1566, 1670, 1269, 1155, 680; 1H NMR
(CDCl3): d 1.82 (s, 6H), 3.91 (s, 3H), 6.52 (dd, J1 = 8.1 Hz,
J2 = 2.1 Hz, 1H), 6.67 (dd, J1 = 8.1 Hz, J2 = 2.1 Hz, 1H), 6.84
(t, J=2.4 Hz, 1H), 7.29 (d, J=7.8 Hz, 1H),7.60 (d, J=8.4 Hz, 1H),
7.81 (d, J=8.4 Hz, 1H), 7.74 (bs, NH, 1H), 7.91 (d, J=6 Hz, 1H),
8.62 (d, J=6 Hz, 1H), 8.39 (s, 1H), 9.32 (s, 1H), 10.10 (s, 1H),
12.90 (bs, NH,1H); 13C NMR (CDCl3): d 28.49, 50.18, 55.44,
99.57, 104.29, 105.69, 106.18, 114.50, 120.98, 119.25, 123.42,
128.64, 130.34, 135.46, 137.95, 139.55, 143.44, 146.25, 153.06,
161.19, 181.29, 184.66; Anal. Calcd. for C23H22N4O: C, 71.48; H,
solution of 17,18 (0.7 mol) and hydroxylamine hydrochloride
(0.048 g, 0.7 mol) in absolute ethanol (15 mL) was stirred at RT
for 2 days. After this time, a yellow precipitate had formed and
was filtered off, washed with water and dried in air. The crude
products 24,25 were purified by recrystallization from EtOH.
4-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)isoxazole (24).
Yield of 65%; mp 295 ꢀC (dec.); FTIR (KBr, cmÀ1) nmax 3099,
1
3055, 3029, 2975, 1634, 1608, 1554, 1680, 1129, 825; H NMR
(DMSO-d6): d 1.57 (s, 6H), 8.28 (d, J=8.4 Hz, 1H), 8.47
(d, J=8.4 Hz, 1H), 8.73 (s, 2H), 9.36(s,1H), 9.90 (s, 1H), 10.05
(s, 1H); 13C NMR (DMSO-d6): d 19.82, 56.01, 114.66, 120.10,
124.92, 127.71, 129.18, 160.89, 163.93, 147.74, 148.77, 149.28,
153.43, 160.45, 189.19; Anal. Calcd. For C16H13N3O: C, 72.99; H,
4.98; N, 15.96% found: C, 72.91; H, 4.89; N, 15.91%.
2-(5-bromo-3,3-dimethyl-1H-pyrrolo[3,2-h]isoquinolin-2(3H)-
ylidene)-3-oxopropanenitrile (25). Yield of 70%; mp
292.0–293.0 ꢀC; FTIR (KBr, cmÀ1) nmax 3201 (NH), 3059, 2205
1
(CN), 1648, 1631, 1544, 1388, 1361, 1165, 887, 758; H NMR
5.74; N, 14.50% found: C, 71.07; H, 5.40; N, 15.01%.
2-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)-2-(2-(4-
(CDCl3): d 1.81 (s, 6H), 7.76 (s, 1H), 8.09 (d, J = 6.0 Hz, 1H),
8.75 (d, J = 6.0 Hz,1H), 9.44 (s, 1H), 9.51 (s, 1H, CHO), 13.10
(bs, NH, 1H); 13C NMR (CDCl3): d 23.36, 50.89, 115.90, 118.69,
124.32, 127.80, 133.34, 134.70, 135.66, 144.99, 146.20, 178.32,
188.04; Anal. Calcd. for C16H12BrN3O: C, 56.16; H, 3.53; N,
12.28% found: C, 56.12; H, 3.52; N; 12.19%.
methylphenyl)hydrazono)-acetaldehyde (21g).
Yield of 70%;
mp 140.0–141.5 ꢀC; FTIR (KBr, cmÀ1) nmax 3268, 2974, 2931,
1602, 1580, 1560, 1670, 1264, 679; 1H NMR (CDCl3): d 1.82
(s, 6H), 2.38 (s, 3H), 7.15 (d, J=8.4 Hz, 2H), 7.19 (d, J=8.4 Hz,
2H), 7.57 (bs, NH, 1H), 7.60 (d, J=8.4 Hz, 1H), 8.41 (d, J=5.7 Hz,
1H), 7.81 (d, J=8.4 Hz, 1H), 8.37 (s, 1H), 8.64 (d, J=5.7 Hz, 1H),
9.33 (s, 1H), 10.09 (s, 1H), 12.91 (bs, NH, 1H); 13C NMR (CDCl3):
d 20.64, 50.16, 106.30, 112.76, 114.14, 118.08, 119.19, 123.37,
128.65, 129.80, 129.99, 135.51, 137.64, 139.60, 142.75, 143.33,
153.18, 181.14, 184.66; Anal. Calcd. for C23H22N4O: C, 74.57; H,
5.99; N, 15.12% found: C, 74.11; H, 5.63; N, 15.60%.
Acknowledgments. The authors are grateful to the University of
Urmia and Urmia University of Technology for financial support
of this work.
2-(5-bromo-3,3-dimethyl-3H-pyrrolo[3,2-H]isoquinolin-2-yl)-
2-(2-(p-tolyl) hydrazono)acetaldehyde (22g). Yield of 65%; mp
230.5–232.5 ꢀC; FTIR (KBr, cmÀ1) nmax 3273, 3120, 2966, 1634,
REFERENCES AND NOTES
1
1612, 1597, 1564, 1657, 1267, 1182, 811; H NMR (CDCl3): d
[1] Friedel, M. C. Bull Soc Chim Fr 1896, 11, 1028.
[2] Fischer, O.; Muller, A.; Vilsmeier, A. J Prakt Chem 1925,
69, 109.
1.81 (s, 6H), 2.34 (s, 3H), 7.05 (d, J=8.4 Hz, 2H), 7.26 (d,
J=8.4 Hz, 2H), 7.55 (bs, NH, 1H), 7.73 (s,1H), 8.06 (dd, J1 =6Hz,
J2 = 0.6 Hz, 1H), 8.33 (s, 1H), 8.72 (d, J=6.0 Hz, 1H), 9.51 (s, 1H,
CHO), 10.10 (d, J=0.6 Hz,1H), 16.02 (bs, NH, 1H); 13C NMR
(CDCl3): d 20.57, 28.66, 58.44, 106.89, 112.76, 115.94, 118.70,
124.59, 125.23, 130.12, 130.18,133.18, 136.83, 137.23, 142.41,
144.46, 146.68, 180.50, 184.75; Anal. Calcd. for C23H21BrN4O: C,
61.48; H, 4.71; N, 12.47% found: C, 61.60; H, 4.39; N, 12.81%.
5-(3,3-dimethyl-3H-pyrrolo[2,3-f]isoquinolin-2-yl)pyrimidine-
2(1H)-thione(23). A solution of 18 (0.2 g, 0.7 mol) and thiourea
(0.053 g, 0.7 mol) in absolute ethanol (15 mL) was treated with
concentrated hydrochloric acid (1 mL), and reaction mixture was
stirred at RT for 2 days. After solvent evaporated, water was
added to the residue, and solution neutralized by solid NaOH.
Obtained solid filtered off, washed with water and dried in air.
The crude product was purified by recrystallization from EtOH.
85% yield; mp 256–258ꢀC; FTIR (KBr, cmÀ1) nmax 3056, 2968,
2873, 2736(SH), 1673, 1647, 1687, 1194(C= S), 1168; 1H NMR
[3] (a) Vilsmeier, A.; Haack, A. Chem Ber 1927, 60, 119;
(b) Vilsmeier, A.; Haack, A. Bull Soc Chim Fr 1962, 77, 1989.
[4] (a) Arnold, Z.; Zemlicka, J. Proc Chem Soc (London) 1958, 4, 227;
(b) Arnold, Z.; Holy, A. Collect Czech Chem Commun 1961, 26, 3059.
[5] For some recent contributions see: (a) Cheng, Y.; Yang, H. B.;
Liu, B.; Meth-Cohn, O.; Watkin, D.; Humphries, S. Synthesis 2003, 35,
906; (b) Cheng, Y.; Jiao, P.; Williams, D. J.; Meth-Cohn, O. Tetrahedron
Lett 1999, 40, 6661.
[6] Jones, G.; Stanforth, S. P. Org React 2000, 56, 355.
[7] Fritz, H. Chem Ber 1959, 92, 1809.
[8] Baradarani, M. M.; Afghan, A.; Zebarjadi, F.; Hasanzadeh, K.;
Joule, J. A. J Heterocycl Chem 2006, 43, 1591.
[9] Rashidi, A.; Afghan, A.; Baradarani, M. M.; Joule, J. A. J
Heterocycl Chem 2009, 46, 428.
[10] Helliwell, M.; Afghan, A.; Baradarani, M. M.; Joule, J. A.
Acta Crystallogr Sect E 2006, E62, o737.
[11] Helliwell, M.; Afghan, A.; Keshvari, F.; Baradarani, M. M.;
Joule, J. A. Acta Crystallogr Sect E 2010, E66, o112.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet