Facile synthesis of hydrazine derivatives of 5H-pyrrolo[3,4-b]pyrazine and 1H-pyrrolo[3,4-b]quinoxaline

Article abstract of DOI:10.1055/s-0033-1340042

A convenient and efficient route for the chemoselective synthesis of carbohydrazide, arenesulfonylhydrazide, and thiosemicarbazone derivatives of 5H-pyrrolo[3,4-b]pyrazine and 1H-pyrrolo[3,4-b]quinoxaline from the corresponding dinitriles and substituted hydrazines was elaborated. The synthesis of starting pyrazine-2,3-dicarbonitrile was sufficiently improved by using concentrated HCl as a catalyst. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0033-1340042

PAPER
▌3375
paper
Facile Synthesis of Hydrazine Derivatives of 5H-Pyrrolo[3,4-b]pyrazine and
1H-Pyrrolo[3,4-b]quinoxaline
5H-Pyrrolo[3,4-b]pyrazine and 1H-Pyrrolo[3,4-b]quinoxaline
Olga V. Hordiyenko,*a Igor V. Rudenko,a Irina A. Zamkova,a Oleksandr V. Denisenko,a Angelina V. Biitseva,a
Axelle Arrault,b Andrei A. Tolmacheva
a
Taras Shevchenko National University of Kyiv, vul. Volodymyrs’ka, 64/13, Kyiv 01601, Ukraine
Fax +380(44)2351273; E-mail: ov_hordiyenko@univ.kiev.ua
b
Laboratoire de Chimie Physique Macromoléculaire, INPL, ENSIC, 1 rue Grandville, 54001 Nancy Cedex, France
Received: 03.07.2013; Accepted after revision: 26.09.2013
The benzo analogue of 1, the dicarbonitrile 2, reacts with
Abstract: A convenient and efficient route for the chemoselective
ammonia in a similar manner.14 Special attention has been
synthesis of carbohydrazide, arenesulfonylhydrazide, and thiosemi-
paid to the reaction of 2 and its ring-substituted analogues
carbazone derivatives of 5H-pyrrolo[3,4-b]pyrazine and 1H-pyrro-
lo[3,4-b]quinoxaline from the corresponding dinitriles and
with hydrazine15 leading to pyridazino[4,5-b]quinoxaline
substituted hydrazines was elaborated. The synthesis of starting derivatives, which are considered as having the structure
similar to the benzopteridines.16 Furan ring closure pro-
pyrazine-2,3-dicarbonitrile was sufficiently improved by using con-
centrated HCl as a catalyst.
ceeded on treatment of 2 with acetophenone,17 and a ditet-
razole quinoxaline derivative was formed with NaN3.18
Key words: heterocycles, nitriles, cyclization, chemoselectivity,
hydrazones
Following our previous research on the synthesis of car-
bohydrazides by interaction of (hetero)aromatic 1,2-di-
carbonitriles with N-acylhydrazines,19,20 we tested the
pyrazine and quinoxaline based dinitriles 1 and 2 in these
reactions. Recently, one example of 5H-pyrrolo[3,4-
Heterocyclic 1,2-dicarbonitriles are widely used in con-
temporary technologies.1 For example, they are used for
the production of azaphthalocyanine containing durable
b]pyrazine carbohydrazide 3 (R = 2-pyridyl) was de-
dyes,2 novel materials for nonlinear optics,3 photo- and
scribed among a series of other carboxydrazides (Figure
semiconductors,4 OLED emitting materials,5 electropho-
1). They were synthesized by our method19 for biological
tographic photoreceptors,6 liquid crystals, electrolumines-
screening, after some of the phthalonitrile-derived carbo-
cent devices,7 solar energy conversion devices, and
hydrazides were shown to have a pronounced herbicidal
photoselective absorbing filters for color display devices.8
and antimalarial activity.21
Besides, 2,3-dicyanoazines are also useful building
Contrary to the reaction of N-acylhydrazines with 4,6-di-
blocks for the preparation of fused heterocycles. Howev-
methylpyridine-2,3-dicarbonitrile studied before, where
er, despite their potential, the cyclization reactions of pyr-
formation of regioisomers was observed,20 similar con-
azine-2,3-dicarbonitrile (1) and quinoxaline-2,3-
densation of dicarbonitriles 1 and 2 is devoid of the selec-
dicarbonitrile (2) (Figure 1) with N-nucleophiles were
tivity problem. At the same time, unlike the reactions of
the phthalonitrile, this interaction could be complicated by
nucleophilic substitution of the cyano group activated by
nitrogen atoms of the heterocyclic core. There are known
examples of such reactions for dinitrile 1 as well as for 2
described in the literature. One of the nitrile groups in 1
poorly studied thus far. There are a few literature exam-
ples on the use of dinitriles 1 and 2 for the preparation of
heterocycles. Typical for 1 is the ammonolysis with pyr-
roline ring closure via the corresponding alkoxy
derivatives9 or by hydrolysis with further amination.10
Similar transformations involving amines11 and
was indeed replaced with amine, for example, methyl-
diamines12 and formation of pyrazino[2,3-d]pyridazine-
amine at room temperature in THF in the presence of
5,8-diamine in the reaction with hydrazine13 were de-
triethylamine22 and allylamine on simple treatment23 in
scribed.
the synthesis of pteridinone derivatives;24 however, ben-
zylamine and n-butylamine required reflux in DMF.11 On
NHC(O)R
N
treatment with alcohols one alkoxy group was introduced
N
N
CN
CN
N
N
CN
CN
in place of a nitrile group in 1 similar to 2.11 In the reac-
tions of 2 with thiols both cyano groups underwent substi-
tution.25 Taking into account these facts, the reaction
conditions of 1 and 2 with N-acylhydrazines minimizing
the side reactions can be elaborated.
N
N
N
NH2
1
2
3
Figure 1 Pyrazine-2,3-dicarbonitrile (1), quinoxaline-2,3-dicarboni-
trile (2), and 5H-pyrrolo[3,4-b]pyrazinecarbohydrazides 3
We aimed first at the optimization of the known methods
for the synthesis of starting dinitriles 1 and 2. Among the
approaches tested,14a,b,16,17,26–31 the method starting from
diaminomaleonitrile (DAMN) was found to be the most
efficient affording 1 in the reaction with glyoxal14a,30 and
SYNTHESIS 2013, 45, 3375–3382
Advanced online publication: 06.11.2013
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DOI: 10.1055/s-0033-1340042; Art ID: SS-2013-Z0454-OP
© Georg Thieme Verlag Stuttgart · New York

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O. V. Hordiyenko et al.
PAPER
1. DDQ
N
N
CN
CN
H2N
H2N
CN
CN
N
N
CN
CN
40% aq (CHO)2, HCl (cat.)
2. 1,2-(NH2)2C6H4
EtOH,
reflux, 30 min, >90%
65%
1
2
Scheme 1 Synthesis of pyrazine-2,3-dicarbonitrile (1) and quinoxaline-2,3-dicarbonitrile (2)
2 with o-phenylenediamine14a,31a (Scheme 1). Compound in the similar way as to 1, from DAMN via oxidation with
1 could be obtained according to the literature protocol DDQ to diiminosuccinonitrile31b and further reaction with
from a mixture of DAMN with equimolar amount of 40% o-phenylenediamine by the known protocol.14a,31a The lat-
aqueous glyoxal for 15–30 minutes in the presence of ter procedure enabled the preparation of 2 in a satisfactory
14a
AcOH30a or (CO2H)2 as a catalyst in refluxing ethanol yield of 65%.
in about 60% yield. The basic t-BuOK catalysis can also
Next, conditions for the reaction of dinitriles 1 and 2 with
be used for the synthesis of dinitrile 1 in good yield over
N-acylhydrazines possessing alkyl, aryl, or heteroaryl
80% although the isolation of the desired product required
moieties were elaborated (Table 1). Various solvents
(MeOH, i-PrOH, n-BuOH), temperature, and catalysts
(K2CO3, CaCl2, KF, Et3N, NaOMe) were tested for 1. The
best yields of N′-(7-amino-5H-pyrrolo[3,4-b]pyrazin-5-
ylidene)carbohydrazides 3a–m were achieved by the ad-
dition of dinitrile 1 to a prepared mixture of the corre-
sponding hydrazine derivative with a catalytic amount of
liquid chromatography for its purification.30b We im-
proved the known procedures14a,30a significantly by
changing the catalyst to concentrated HCl. After refluxing
for 30 minutes, pure final product crystallized from the
mixture on cooling to room temperature in 90% yield; no
additional purification was needed.
Attempted synthesis of quinoxaline-2,3-dicarbonitrile (2) NaOMe in MeOH upon vigorous stirring. The stirring was
by reported condensation of o-phenylenediamine with ox- continued at room temperature for 0.5–1.5 hours until the
alic acid followed by chlorination with SOCl2 and subse- complete precipitation of the product. Prolongation of re-
quent cyanation14b,32 was found to be inefficient because action time did not improve the yields of the products, be-
of the poor yield in the last step. Variation of cyanides ing in most cases about 90%. It should be noted that
(KCN, CuCN), solvents (DMSO, DMF, pyridine), and changing the addition order significantly decreased the
temperature did not increase the yield of 2 higher than yields of the products.
10%. Therefore, we turned to the preparation of dinitrile 2
Table 1 N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)carbohydrazides 3a–m and N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-yli-
dene)carbohydrazides 4a–k Prepared
NNHC(O)R3
R2
R1
N
N
CN
CN
R2
R1
N
N
NH2NHC(O)R3
NaOMe, MeOH
N
NH2
1 R1 = R2 = H
3a–m R1 = R2 = H
2 R1–R2 = (CH)4
4a–k R1–R2 = (CH)4
Entry
R3
Product
Yield (%)
Entry
R3
Product
Yield (%)
1
2
Me
3a
3b
3c
3d
3e
3f
91
87
89
90
95
87
81
90
94
74
89
73
13
14
15
16
17
18
19
20
21
22
23
24
pyridin-4-yl
Me
3m
4a
4b
4c
4d
4e
4f
71
86
78
72
68
85
83
74
79
66
78
84
i-Pr
3
cyclopropyl
Bn
i-Pr
4
cyclopropyl
Bn
5
adamantan-1-yl
4-MeC6H4
4-EtC6H4
6
adamantan-1-yl
Ph
7
3g
3h
3i
8
4-FC6H4
4-FC6H4
4-ClC6H4
3-SO2NEt2C6H4
pyridin-3-yl
pyridin-4-yl
4g
4h
4i
9
4-BrC6H4
10
11
12
3-SO2NMe2C6H4
2,4-(MeO)2C6H4
pyridin-3-yl
3j
3k
3l
4j
4k
Synthesis 2013, 45, 3375–3382
© Georg Thieme Verlag Stuttgart · New York

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5H-Pyrrolo[3,4-b]pyrazine and 1H-Pyrrolo[3,4-b]quinoxaline
3377
NHSO2Ar
N
N
5a, Ar = Ph (85%)
5b, Ar = 4-FC6H4 (79%)
ArSO2NHNH2
N
N
NH2
H
R2
R1
N
CN
CN
S
S
NH2
N
H
NH
NH
N
N
1, 2
N
R2
R1
N
N
R2
R1
N
N
NH2C(S)NHNH2
N
N
NH2
NH2
6, R1 = R2 = H (91%); 7, R1–R2 = (CH)4 (82%)
Scheme 2 Synthesis of arenesulfonylhydrazides 5 and thiosemicarbazones 6 and 7
Reaction of 2 with N-acylhydrazines was also more effi- Similar to N′-(3-amino-1H-isoindol-1-ylidene)alkylcar-
cient in MeOH solution in the presence of NaOMe, by re- bohydrazides,19 the isomeric ratio of Z- and E-amide
fluxing the reaction mixture till complete precipitation of forms for the studied compounds depends on the solvent
the solid products, except for acetic acid 4a and cyclopro- polarity, Z-form being favored in polar solvents (Table 2).
panecarboxylic acid 4b derivatives where the final solu- Only single isomers assigned to the Z-form were detected
tion was evaporated to afford the crystalline residue. The in the NMR spectra of adamantyl, aromatic, and hetero-
cyclization products, N′-(3-amino-1H-pyrrolo[3,4-b]qui- aromatic acid derivatives 3e–m and 4e–k. Similar to 1H-
noxalin-1-ylidene)carbohydrazides 4a–k with different isoindole derivatives, protons of NH2 group of quinoxa-
acyl residues were isolated in 66–86% yields and purified line series 4a–k showed two singlets in 1H NMR spectra,
by recrystallization from alcohols or DMF.
while the alkyl derivatives 4a–d exhibited four singlets. It
is reasonable to conclude that compounds 4a–k exhibit
considerable contribution of bipolar structure in solution
(Scheme 3) as it was shown for 1H-isoindole derivatives
Using the elaborated procedures, arenesulfonylhydrazides
5 and thiosemicarbazone derivatives 6 and 7 were synthe-
sized in high yields (Scheme 2). It should be noted that
like in the case of phthalonitrile19,20 all transformations
proceeded chemoselectively. Even if two equivalents of
hydrazine derivative were introduced into the reaction
with 1 or 2, only the products with one hydrazone residue
3–7 were isolated. No other substitution products were
observed, judging from the LC/MS data of the crude prod-
ucts.
Table 2 Influence of the Solvent Polarity on the Z/E Isomeric Ratio
of Compounds 3a–d and 4a–d
Entry
Compound
Z/E ratio
In DMSO-d6–
In DMSO-d6–
CCl4 (1:0)
CCl4 (1:1)
1
2
3
4
5
6
7
8
3a, R = Me
3b, R = i-Pr
3c, R = c-Pr
3d, R = Bn
4a, R = Me
4b, R = i-Pr
4c, R = c-Pr
4d, R = Bn
1:1.45
1:1.10
1:0.90
1:0.75
1:1.45
1:0.85
1:0.90
1:0.70
1:2.75
1:2.30
1:1.50
1:1.60
1:2.55
1:1.45
1:1.75
1:1.25
Similar to their non-aza analogues,19 the most probable
tautomeric forms of derivatives 3a–m and 4a–k could be
supposed to adopt less strained Z-configuration at hydra-
zone C=N bond. Minor low field shift of hydrazone NH
signals in the series of compounds 3 and 4 compared to
1Н-isoindole analogues19 could be explained by the influ-
ence of the nitrogen atoms of the pyrazine ring, rather than
hydrogen bonding formation. In addition, N–CO amide
isomers in DMSO-d6 solutions of compounds 3a–d and
4a–d possessing alkyl substituent at carbonyl group re-
vealed two sets of signals in the 1H and 13C NMR spectra
(Scheme 3).
O
R
R
O
Z
E
Z/E
N
N
N
NHC(O)R
N
N
H
H
R2
R1
N
N
R2
R1
N
N
R2
R1
N
N
Z
Z
Z
N
N
N
NH2
NH2
N
H
H
3, R1 = R2 = H; 4, R1–R2 = (CH)4
Scheme 3 Z- and E-amide isomers of carbohydrazides 3 and 4
© Georg Thieme Verlag Stuttgart · New York
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O. V. Hordiyenko et al.
PAPER
with DDQ,31b followed by reaction with o-phenylenediamine in
TFA; grey crystals (from MeCN); yield 65%; mp 218 °C (Lit.14a mp
219 °C; Lit.31a mp 218–220 °C).
by means of 2D NMR experiments, X-ray diffraction, and
quantum calculations.19,33
In the pyrazine series 3a–m, the contribution of bipolar
structure could be recognized by the presence of broad
signals of the protons of NH2 group due to fast proton ex-
change in their 1H NMR spectra.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)carbohydra-
zides 3a–m; General Procedure
To a stirred solution of the respective acid hydrazide (3.5 mmol) in
anhydrous MeOH (30 mL) was added NaOMe (0.35 mL, 1 N solu-
tion in MeOH). After 5 min, pyrazine-2,3-dicarbonitrile (1; 0.46 g,
3.5 mmol) was added in one portion and the stirring was continued
for 0.5–1.5 h at r.t. The precipitate formed was collected by filtra-
tion, washed with hexane (5 mL), recrystallized from MeOH or
EtOH, and dried under vacuum.
No amide isomeric forms could be derived for benzene-
1
sulfonylhyrdrazones 5a,b, and their H NMR spectra
demonstrated one set of signals. In the 1H NMR spectra of
7-amino-5H-pyrrolo[3,4-b]pyrazin-5-one thiosemicarba-
zone 6 and 3-amino-1H-pyrrolo[3,4-b]quinoxalin-1-one
thiosemicarbazone 7 broad signals of NH and NH2 pro-
tons connected to pyrrole ring were observed due to pos-
sible exchange processes.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)acetohydra-
zide (3a)
Yield: 0.66 g (91%); pale brown solid; mp 262–264 °C (MeOH).
IR (KBr): 1171, 1262, 1517, 1677, 3183, 3409 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 2.08 and 2.29 (2 s, 3 H, CH3),
8.65 (br s, 2 H, NH2), 8.71–8.77 (m, 2 H, Hpyraz), 9.70 and 10.69 (2
br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): δ = 20.6, 22.3, 144.4, 144.5,
146.2, 148.1, 148.2, 149.3, 150.9, 151.5, 152.1, 163.8, 164.0, 166.5,
171.5, 173.9.
The most characteristic are the proton signals of the NH2
group of the thioamide moiety, which were observed as
two singlets with the chemical shift differences ranging
from 0.5 to 0.8 ppm. Similar to previously observed be-
havior of 2-(3-amino-1H-isoindol-1-ylidene)hydrazine
carbothioamide,34 we consider this structure as a resonant
hybrid with significant contribution of bipolar structure MS (CI): m/z (%) = 205 (100, [M + H+]).
with positive charge at the N atom (Scheme 2).35
Anal. Calcd for C8H8N6O (204.19): C, 47.06; H, 3.95; N, 41.16.
Found: C, 47.39; H, 4.09; N, 41.32.
In summary, we have elaborated an efficient synthetic
route for the novel carbohydrazide, arenesulfonylhydra-
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-2-methyl-
zide, and thiosemicarbazone derivatives of 5H-pyrro- propanohydrazide (3b)
Yield: 0.71 g (87%); yellow solid; mp 288–290 °C (MeOH).
lo[3,4-b]pyrazine and 1H-pyrrolo[3,4-b]quinoxaline 3–7
avoiding possible side reactions. The key compounds in
the synthesis were pyrazine-2,3-dicarbonitrile (1) and qui-
IR (KBr): 1164, 1515, 1653, 1671, 2968, 3190, 3375 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 1.07 and 1.11 [2 d, J = 6.8 Hz,
noxaline-2,3-dicarbonitrile (2). Synthetic protocol for 1 6 H, CH(CH3)2], 2.75–2.82 and 3.42–3.49 (2 m, 1 H, CH), 8.63–
8.77 (m, 4 H, NH2 + Hpyraz), 9.52 and 10.58 (2 br s, 1 H, NH).
was improved significantly by changing the catalyst to
13C NMR (100 MHz, DMSO-d6): δ = 19.4, 20.2, 30.1, 33.3, 144.6,
144.7, 146.4, 146.5, 148.3, 148.5, 149.6, 151.6, 151.7, 152.2, 164.0,
164.2, 173.6, 177.7.
concentrated HCl that enhanced the yield up to 90%. Het-
erocyclization of dinitriles 1 and 2 proceeded chemoselec-
tively, only one hydrazone residue was introduced into the
final molecules 3–7. The amidine moiety of compounds
3–7 can be used for their further transformations, which
are ongoing in our laboratory.
MS (CI): m/z (%) = 233 (100, [M + H+]).
Anal. Calcd for C10H12N6O (232.24): C, 51.72; H, 5.21; N, 36.19.
Found: C, 52.01; H, 5.32; N, 36.33.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)cyclopro-
panecarbohydrazide (3c)
Chemicals of commercial grade were used without further purifica-
tion. MeOH was dried according to standard procedures. Melting
points were determined on a Boetius microscope hot plate appara-
tus. Elemental analyses (C, H, N) were conducted using the Vario
Micro Cube. Mass spectra were recorded on an Agilent 1100 LC-
MSD SL instrument by chemical ionization (CI). IR spectra were
recorded with a PerkinElmer Spectrum BX FTIR spectrometer. 1H
NMR and 13С NMR spectra were recorded on Mercury (Varian) 400
spectrometer (400 MHz 1H and 100 MHz for 13С) with TMS as in-
ternal standard.
Yield: 0.72 g (89%); pale brown solid; mp 272–273 °C (MeOH).
IR (KBr): 1165, 1213, 1319, 1522, 1608, 1631, 1672, 3189, 3454
cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 0.79–0.94 [m, 4 H, (CH2)2],
2.11 and 2.70 (2 br s, 1 H, CH), 8.53–8.81 (m, 4 H, NH2 + Hpyraz),
9.62 and 10.99 (2 br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): δ = 7.7, 8.5, 10.3, 13.1, 144.2,
144.4, 146.1, 148.0, 148.1, 149.5, 150.5, 151.4, 152.1, 163.6, 163.9,
170.2, 174.2.
Pyrazine-2,3-dicarbonitrile (1)
MS (CI): m/z (%) = 231 (100, [M + H+]).
DAMN (20 g, 185 mmol) was dissolved in boiling EtOH (120 mL)
and 40% aq glyoxal solution (30 mL, 2 mmol) was added. After stir-
ring the mixture, concd HCl (3 mL) was added and the refluxing
was continued for 30 min. The mixture was cooled to r.t. and the
precipitated crystalline solid was collected by filtration, washed
with EtOH (30 mL), hexane (30 mL), and dried on air to give 1 as a
colorless solid; yield: 22 g (91%); mp 133–134 °C (Lit.14a,31 mp
130–135 °C).
Anal. Calcd for C10H10N6O (230.23): C, 52.17; H, 4.38; N, 36.50.
Found: C, 52.29; H, 4.48; N, 36.68.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-2-phenyl-
acetohydrazide (3d)
Yield: 0.89 g (90%); pale brown solid; mp 236–238 °C (MeOH).
IR (KBr): 1155, 1172, 1365, 1492, 1663, 1678, 3179, 3325 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 3.76 and 4.07 (2 s, 2 H, CH2),
7.24–7.33 (m, 5 H, C6H5), 8.69–9.14 (m, 5 H, NH2 + Hpyraz + NH).
Quinoxaline-2,3-dicarbonitrile (2)
This compound was prepared according to the literature
procedure14a,31a from DAMN via oxidation to diiminosuccinonitrile
Synthesis 2013, 45, 3375–3382
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5H-Pyrrolo[3,4-b]pyrazine and 1H-Pyrrolo[3,4-b]quinoxaline
3379
13C NMR (100 MHz, DMSO-d6): δ = 39.3, 41.7, 127.1, 127.2,
128.9, 129.0, 129.9, 130.3, 144.6, 144.7, 146.4, 148.4, 148.6, 149.9,
151.8, 151.9, 152.3, 164.2, 164.4, 167.7, 172.1.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-4-bromo-
benzohydrazide (3i)
Yield: 1.15 g (94%); brown solid; mp 255 °C (EtOH).
IR (KBr): 1147, 1316, 1505, 1655, 3126, 3301, 3458 cm–1.
MS (CI): m/z (%) = 281 (100, [M + H+]).
1H NMR (400 MHz, DMSO-d6): δ = 7.61 (d, J = 6.4 Hz, 2 Harom),
7.99 (d, J = 6.4 Hz, 2 Harom), 8.62 (s, 1 Hpyraz), 8.64 (s, 1 Hpyraz).
13C NMR (100 MHz, DMSO-d6): δ = 124.1, 130.5, 131.2, 143.7,
145.3, 147.2, 150.8, 151.8. 162.9.
MS (CI): m/z (%) = 346 (100, [M + H+]).
Anal. Calcd for C14H12N6O (280.28): C, 59.99; H, 4.32; N, 29.98.
Found: C, 60.30; H, 4.56; N, 29.76.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)adamantane-
1-carbohydrazide (3e)
Yield: 1.09 g (95%); brownish solid; mp 303 °C (MeOH).
IR (KBr): 1173, 1499, 1656, 2850, 2906, 3057, 3180, 3349 cm–1.
Anal. Calcd for C13H9BrN6O (345.15): C, 45.24; H, 2.63; N, 24.35.
Found: C, 45.18; H, 2.60; N, 24.26.
1H NMR (400 MHz, DMSO-d6): δ = 1.75 (br s, 6 H, 3 CH2), 1.95
(br s, 6 H, 3 × CH2), 2.06 (br s, 3 H, 3 × CH), 8.55 (br s, 2 H, NH2),
8.69 (s, 1 Hpyraz), 8.77 (s, 1 Hpyraz), 10.09 (s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): δ = 28.0, 36.5, 39.1, 144.5, 146.5,
148.3, 151.7, 152.6, 164.0, 172.5.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-3-[(dimeth-
ylamino)sulfonyl]benzohydrazide (3j)
Yield: 0.98 g (74%); brownish solid; mp 250 °C (EtOH).
IR (KBr): 1162, 1340, 1517, 1609, 1649, 1676, 3187, 3422 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 2.71 [s, 6 H, N(CH3)2], 7.86 (t,
J = 7.6 Hz, 1 Harom), 8.00 (d, J = 7.6 Hz, 1 Harom), 8.25 (d, J = 8 Hz,
2 Harom), 8.79 (s, 1 Hpyraz), 8.86 (s, 1 Hpyraz), 9.44 (br s, 3 H, NH2 +
NH).
MS (CI): m/z (%) = 225 (99, [M + H+]).
Anal. Calcd for C17H20N6O (324.38): C, 62.95; H, 6.21; N, 25.91.
Found: C, 63.12; H, 6.31; N, 26.09.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-4-methyl-
benzohydrazide (3f)
13C NMR (100 MHz, DMSO-d6): δ = 38.2, 126.7, 130.3, 130.7,
132.1, 135.3, 135.9, 144.8, 146.5, 148.4, 151.9, 153.7, 162.2, 164.4.
MS (CI): m/z (%) = 374 (98, [M + H+]).
Yield: 0.86 g (87%); pale yellow solid; mp 269 °C (EtOH).
IR (KBr): 1171, 1281, 1544, 1678, 3152, 3469 cm–1.
Anal. Calcd for C15H15N7O3S (373.39): C, 48.25; H, 4.05; N, 26.26.
Found: C, 48.09; H, 3.97; N, 26.34.
1H NMR (400 MHz, DMSO-d6): δ = 2.37 (s, 3 H, CH3), 7.34 (d,
J = 6.8 Hz, 2 Harom), 7.77 (d, J = 6.8 Hz, 2 Harom), 8.73 (s, 1 Hpyraz),
8.80 (s, 1 Hpyraz), 9.41 (br s, 3 H, NH2 + NH).
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 127.5, 129.7, 130.7,
142.5, 144.5, 146.3, 148.3, 151.8, 153.1, 162.4, 164.0.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-3,4-di-
methoxybenzohydrazide (3k)
Yield: 1.03 g (89%); orange solid; mp 250 °C (EtOH).
IR (KBr): 1136, 1153, 1353, 1487, 1652, 3157, 3375 cm–1.
MS (CI): m/z (%) = 281 (100, [M + H+]).
1H NMR (400 MHz, DMSO-d6): δ = 3.86 (s, 3 H, OCH3), 3.87 (s, 3
H, OCH3), 7.07 (d, J = 8.4 Hz, 1 Harom), 7.59 (br s, 2 Harom), 8.66 (s,
1 Hpyraz), 8.70 (s, 1 Hpyraz).
Anal. Calcd for C14H12N6O (280.28): C, 59.99; H, 4.32; N, 29.98.
Found: C, 59.87; H, 4.30; N, 29.92.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-4-ethylben-
zohydrazide (3g)
13C NMR (100 MHz, CF3CO2D): δ = 54.9, 55.2, 110.9, 111.0,
121.6, 122.3, 139.3, 141.0, 142.3, 148.4, 148.5, 150.3, 153.8, 158.5,
166.6.
Yield: 0.84 g (81%); pale yellow solid; mp 230 °C (EtOH).
IR (KBr): 1542, 1638, 1681, 2922, 3150 cm–1.
MS (CI): m/z (%) = 327 (96, [M + H+]).
1H NMR (400 MHz, DMSO-d6): δ = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
2.69 (q, J = 7.2 Hz, 2 H, CH2), 7.32 (d, J = 7.2 Hz, 2 Harom), 7.80 (br
s, 2 Harom), 8.69 (s, 1 Hpyraz), 8.76 (s, 1 Hpyraz), 9.09 (br s, 3 H, NH2
+ NH).
13C NMR (100 MHz, DMSO-d6): δ = 15.6, 28.7, 127.5, 128.2,
131.1, 144.1, 146.0, 148.3, 151.8, 152.5, 162.1, 163.7.
Anal. Calcd for C15H14N6O3 (326.31): C, 55.21; H, 4.32; N, 25.75.
Found: C, 55.15; H, 4.39; N, 25.89.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)nicotinohy-
drazide (3l)
Yield: 0.69 g (73%); brownish solid; mp 238 °C (EtOH).
IR (KBr): 1152, 1290, 1474, 1536, 1654, 3172, 3323, 3518 cm–1.
MS (CI): m/z (%) = 295 (100, [M + H+]).
1H NMR (400 MHz, DMSO-d6): δ = 7.46–7.48 (m, 1 Hpy), 8.34 (d,
J = 6.0 Hz, 1 Hpy), 8.64–8.70 (m, 3 H, Hpy + Hpyraz), 9.18 (s, 1 Hpyraz).
13C NMR (100 MHz, DMSO-d6): δ = 124.0, 131.7, 135.9, 144.5,
146.2, 148.0, 149.5, 152.1, 152.4, 163.8, 164.8.
MS (CI): m/z (%) = 268 (100, [M + H+]).
Anal. Calcd for C15H14N6O (294.31): C, 61.21; H, 4.79; N, 28.55.
Found: C, 61.39; H, 4.89; N, 28.42.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-4-fluoroben-
zohydrazide (3h)
Yield: 0.90 g (90%); brownish solid; mp 270 °C (EtOH).
IR (KBr): 1159, 1178, 1237, 1498, 1604, 1655, 3192, 3464 cm–1.
Anal. Calcd for C12H9N7O (267.25): C, 53.93; H, 3.39; N, 36.69.
Found: C, 53.88; H, 3.47; N, 36.74.
1H NMR (400 MHz, DMSO-d6): δ = 7.42 (t, J = 8 Hz, 2 Harom), 8.00
(br s, 2 Harom), 8.78 (s, 1 Hpyraz), 8.85 (s, 1 Hpyraz), 9.48 (br s, 3 H,
NH2 + NH).
13C NMR (100 MHz, DMSO-d6): δ = 116.0, 116.2, 130.3, 130.5,
139.9, 144.6, 146.4, 148.4, 151.8, 163.6, 164.2, 165.6.
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)isonicotino-
hydrazide (3m)
Yield: 0.67 g (71%); red-brownish solid; mp 247 °C (EtOH).
IR (KBr): 1156, 1333, 1501, 1670, 3173, 3370 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.97 (d, J = 4.0 Hz, 2 Hpy),
MS (CI): m/z (%) = 285 (98, [M + H+]).
8.56–8.59 (m, 4 H, Hpy + Hpyraz).
13C NMR (100 MHz, DMSO-d6): δ = 122.7, 140.6, 143.4, 145.1,
Anal. Calcd for C13H9FN6O (284.25): C, 54.93; H, 3.19; N, 29.57.
Found: C, 54.83; H, 3.07; N, 29.49.
146.5, 147.6, 149.6, 149.7, 151.8, 162.0.
MS (CI): m/z (%) = 268 (100, [M + H+]).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3375–3382

3380
O. V. Hordiyenko et al.
PAPER
Anal. Calcd for C12H9N7O (267.25): C, 53.93; H, 3.39; N, 36.69.
Found: C, 53.97; H, 3.51; N, 36.59.
Hquin), 8.51, 8.83, 8.87, and 8.91 (4 br s, 2 H, NH2), 9.83 and 10.85
(2 br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 41.2, 128.4, 128.3, 129.4,
128.7, 130.1, 130.6, 134.9, 135.4, 138.6, 139.8, 140.0, 142.9, 143.9,
159.1, 173.4.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)carbohy-
drazides 4a–k; General Procedure
Quinoxaline-2,3-dicarbonitrile (2; 0.63 g, 3.5 mmol) was dissolved
by heating in anhydrous MeOH (30 mL) and the corresponding acid
hydrazide (3.5 mmol) and NaOMe (0.35 mL, 1 N solution in
MeOH) were added. The resulting mixture was refluxed with stir-
ring for 4–6 h. After cooling, the precipitate formed was collected
by filtration and washed with MeOH (5 mL). Recrystallization from
MeOH, EtOH, or DMF afforded 4a–k.
MS (CI): m/z (%) = 331 (100, [M + H+]).
Anal. Calcd for C18H14N6O (330.34): C, 65.44; H, 4.27; N, 25.44.
Found: C, 65.60; H, 4.46; N, 25.66.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)adaman-
tane-1-carbohydrazide (4e)
Yield: 1.11 g (85%); yellow solid; mp 318–320 °C (EtOH).
IR (KBr): 1177, 1498, 1678, 2902, 3183, 3340, 3462 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 1.72 (br s, 6 H, 3 × CH2), 1.92
(br s, 6 H, 3 × CH2), 2.04 (br s, 3 H, 3 × CH), 7.96–8.03 (m, 2 Hquin),
8.24 (d, J = 8 Hz, 1 Hquin), 8.28 (d, J = 8 Hz, 1 Hquin), 8.96 (br s, 2
H, NH2), 10.09 (br s, 1 H, NH).
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)acetohy-
drazide (4a)
Yield: 0.76 g (86%); greenish solid; mp 304–306 °C (MeOH).
IR (KBr): 1184, 1213, 1518, 1611, 1678, 3178, 3359 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 2.10 and 2.33 (2 s, 3 H, CH3),
7.98 (br s, 2 Hquin), 8.23–8.29 (m, 2 Hquin), 8.83 (br s, 2 H, NH2), 9.68
and 10.73 (2 br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 29.2, 37.0, 40.1, 42.6, 131.2,
132.2, 136.7, 137.7, 140.9, 141.8, 145.0, 145.6, 167.0, 181.2.
MS (CI): m/z (%) = 375 (100, [M + H+]).
13C NMR (100 MHz, DMSO-d6): δ = 20.7, 22.2, 130.1, 130.5,
131.4, 132.1, 141.3, 142.3, 142.4, 147.7, 147.9, 149.1, 150.1, 150.5,
150.7, 164.0, 164.1, 166.4, 171.4.
Anal. Calcd for C21H22N6O (374.44): C, 67.36; H 5.92; N, 22.44.
Found: C, 67.44; H, 6.08; N, 22.61.
MS (CI): m/z (%) = 255 (96, [M + H+]).
Anal. Calcd for C12H10N6O (254.25): C, 56.69; H, 3.96; N, 33.05.
Found: C, 56.83; H, 4.06; N, 33.26.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)benzohy-
drazide (4f)
Yield: 0.92 g (83%); yellow solid; mp 323 °C (DMF).
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)-2-meth-
ylpropanohydrazide (4b)
Yield: 0.77 g (78%); greenish solid; mp 290–292 °C (MeOH).
IR (KBr): 1183, 1521, 1625, 1677, 2968, 3186, 3351, 3454 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 1.10 and 1.15 [2 d, J = 6.8 Hz,
6 H, CH(CH3)2], 2.77–2.84 and 3.48–3.57 (2 m, 1 H, CH), 7.95–
8.03 (m, 2 Hquin), 8.23–8.33 (m, 2 Hquin), 8.79 (br s, 2 H, NH2), 9.59
and 10.60 (2 br s, 1 H, NH).
IR (KBr): 1478, 1515, 1668, 1683, 3182, 3345 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.56–7.71 (m, 3 H, C6H5), 7.90
(d, J = 7.2 Hz, 2 H, C6H5), 7.98–8.05 (m, 2 Hquin), 8.26 (d, J = 8 Hz,
1 Hquin), 8.31 (d, J = 8 Hz, 1 Hquin), 8.98 and 9.08 (2 br s, 2 H, NH2),
10.75 (br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 129.4, 130.0, 130.6, 131.7,
132.4, 135.2, 136.4, 139.3, 140.4, 141.3, 143.5, 143.9, 159.3, 164.9.
13C NMR (100 MHz, DMSO-d6): δ = 20.2, 21.5, 30.3, 33.1, 130.0,
130.5, 131.4, 131.9, 141.3, 142.2, 147.7, 148.0, 149.1, 150.2, 150.4,
150.8, 163.8, 164.2, 166.3, 171.5.
MS (CI): m/z (%) = 317 (100, [M + H+]).
Anal. Calcd for C17H12N6O (316.32): C, 64.55; H, 3.82; N, 26.57.
Found: C, 64.69; H, 3.98; N, 26.40.
MS (CI): m/z (%) = 283 (92, [M + H+]).
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)-4-fluoro-
benzohydrazide (4g)
Yield: 0.87 g (74%); yellow solid; mp 324–325 °C (DMF).
Anal. Calcd for C14H14N6O (282.30): C, 59.56; H, 5.00; N, 29.77.
Found: C, 59.69; H, 4.87; N, 29.80.
IR (KBr): 1485, 1668, 1679, 3184, 3339 cm–1.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)cyclopro-
panecarbohydrazide (4c)
1H NMR (400 MHz, DMSO-d6): δ = 7.40 (t, J = 8 Hz, 2 Harom),
7.99–8.09 (m, 4 H, Harom + Hquin), 8.25–8.32 (m, 2 Hquin), 8.96 and
9.08 (2 br s, 2 H, NH2), 10.78 (br s, 1 H, NH).
Yield: 0.71 g (72%); yellow solid; mp 290 °C (EtOH).
IR (KBr): 1502, 1519, 1611, 1673, 3193, 3359, 3519 cm–1.
1H NMR (100 MHz, DMSO-d6): δ = 0.79–0.97 [m, 4 H, (CH2)2],
2.14 and 2.77 (2 br s, 1 H, CH), 7.98–8.01 (m, 2 Hquin), 8.24–8.31
(m, 2 Hquin), 8.47, 8.85, 8.88, and 8.94 (4 br s, 2 H, NH2), 9.80 and
11.06 (2 br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 9.1, 9.9, 13.0, 129.7, 129.9,
130.3, 134.5, 134.9, 135.5, 135.9, 138.6, 139.0, 140.1, 142.7, 143.1,
144.0, 144.3, 159.1, 175.6.
13C NMR (100 MHz, CF3CO2D): δ = 119.0, 119.2, 127.9, 132.3,
132.6, 132.8, 133.3, 137.8, 138.9, 142.1, 143.0, 146.1, 146.6, 162.0,
168.3, 169.1, 170.8.
MS (CI): m/z (%) = 335 (100, [M + H+]).
Anal. Calcd for C17H11FN6O (334.31): C, 61.08; H, 3.32; N, 25.14.
Found: C, 60.88; H, 3.52; N, 24.89.
MS (CI): m/z (%) = 281 (100, [M + H+]).
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)-4-chloro-
benzohydrazide (4h)
Anal. Calcd for C14H12N6O (280.28): C, 59.99; H, 4.32; N, 29.98.
Found: C, 60.30; H, 4.56; N, 29.76.
Yield: 0.97 g (79%); yellow-orange solid; mp 320 °C (DMF).
IR (KBr): 1478, 1512, 1668, 3188, 3201, 3335 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.64 (d, J = 8 Hz, 2 Harom),
7.93 (d, J = 8 Hz, 2 Harom), 7.98–8.07 (m, 2 Hquin), 8.27 (d, J = 8 Hz,
1 Hquin), 8.32 (d, J = 8 Hz, 1 Hquin), 8.97 and 9.09 (2 br s, 2 H, NH2),
10.84 (br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 129.8, 130.0, 130.3, 130.4,
130.6, 130.8, 130.9, 136.4, 139.8, 140.8, 143.7, 144.1, 149.9, 159.6,
166.6.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)-2-phenyl-
acetohydrazide (4d)
Yield: 0.79 g (68%); yellow solid; mp 273 °C (DMF).
IR (KBr): 1494, 1505, 1518, 1613, 1625, 1660, 1679, 3175, 3335
cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 3.77 and 4.12 (2 s, 2 H, CH2),
7.24–7.35 (m, 5 H, C6H5), 7.97–8.01 (m, 2 Hquin), 8.24–8.34 (m, 2
Synthesis 2013, 45, 3375–3382
© Georg Thieme Verlag Stuttgart · New York

PAPER
5H-Pyrrolo[3,4-b]pyrazine and 1H-Pyrrolo[3,4-b]quinoxaline
MS (CI): m/z (%) = 303 (94, [M + H+]).
3381
MS (CI): m/z (%) = 351 (100, [M + H+]).
Anal. Calcd for C17H11ClN6O (350.76): C, 58.21; H, 3.16; N, 23.96.
Found: C, 58.09; H, 3.29; N, 24.18.
Anal. Calcd for C12H10N6O2S (302.31): C, 47.68; H, 3.33; N, 27.80.
Found: C, 47.50; H, 3.24; N, 27.64.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)-3-[(dieth-
ylamino)sulfonyl]benzohydrazide (4i)
Yield: 1.04 g (66%); yellow solid; mp 311 °C (DMF).
N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)-4-fluoroben-
zenesulfonylhydrazide (5b)
Yield: 0.89 g (79%); yellow-orange solid; mp 223–224 °C (EtOH).
IR (KBr): 1338, 1523, 1553, 1607, 1681, 3196, 3326 cm–1.
IR (KBr): 1279, 1648, 3224, 3266, 3309, 3393 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 1.07 (t, J = 7.2 Hz, 6 H,
2 × CH3), 3.22 (q, J = 7.2 Hz, 4 H, 2 × CH2), 7.79 (t, J = 8 Hz, 1
1H NMR (400 MHz, DMSO-d6): δ = 7.24 (t, J = 8 Hz, 2 Harom), 7.43
(br s, 2 H, NH2), 7.83 (br s, 2 Harom), 8.42 (s, 1 Hpyraz), 8.52 (s, 1
H
arom), 7.99–8.06 (m, 3 H), 8.17 (d, J = 8 Hz, 1 H), 8.26–8.34 (m, 3
Hpyraz).
H), 8.95 and 9.10 (2 br s, 2 H, NH2), 11.09 (br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 118.3, 118.5, 132.7, 132.8,
132.9, 142.6, 147.1, 148.8, 149.6, 150.5, 151.5, 152.3, 153.0, 160.3.
MS (CI): m/z (%) = 321 (96, [M + H+]).
13C NMR (100 MHz, CF3CO2D): δ = 12.16 (CH3), 42.11 (CH2),
125.7, 129.9, 130.5, 130.7, 131.6, 132.4, 135.3, 136.4, 139.3, 140.4,
140.7, 141.4, 143.5, 143.8, 159.4, 165.0.
Anal. Calcd for C12H9FN6O2S (320.30): C, 45.00; H, 2.83; N, 26.24.
Found: C, 44.89; H, 2.77; N, 26.34.
MS (CI): m/z (%) = 452 (100, [M + H+]).
Anal. Calcd for C21H21N7O3S (451.50): C, 55.86; H, 4.69; N, 21.72.
Found: C, 56.02; H, 4.77; N, 21.92.
7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-one Thiosemicarbazone
(6)
Yield: 0.71 g (91%); yellow solid; mp 247 °C (EtOH).
IR (KBr): 1489, 1542, 1648, 1653, 1667, 2853, 3155, 3280 cm–1.
1H NMR (100 MHz, DMSO-d6): δ = 7.96 (br s, 1 H, NH), 8.59,
8.72, 8.73, and 9.07 (4 br s, 6 H, 2 × NH, NH2, Hpyraz).
13C NMR (100 MHz, DMSO-d6): δ = 144.7, 146.4, 148.7, 149.6,
151.7, 164.5, 177.8.
MS (CI): m/z (%) = 222 (100, [M + H+]).
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)nicotino-
hydrazide (4j)
Yield: 0.87 g (78%); light yellow solid; mp 315–316 °C (DMF).
IR (KBr): 1481, 1551, 1610, 1684, 3208, 3336 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.57–7.60 (m, 1 Hpy), 7.98–
8.04 (m, 2 H), 8.26–8.33 (m, 2 H), 8.78 (d, J = 4 Hz, 1 Hpy), 8.93,
9.06, and 9.09 (3 br s, 3 H, NH2 + Hpy), 11.05 (br s, 1 H, NH).
13C NMR (100 MHz, CF3CO2D): δ = 124.2, 129.5, 129.8, 130.3,
130.4, 130.8, 136.4, 139.6, 140.6, 142.0, 143.7, 144.2, 149.2, 151.4,
159.8, 166.6.
Anal. Calcd for C7H7N7S (221.24): C, 38.00; H, 3.19; N, 44.32.
Found: C, 38.22; H, 3.22; N, 44.17.
MS (CI): m/z (%) = 318 (100, [M + H+]).
3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-one Thiosemicarba-
zone (7)
Anal. Calcd for C16H11N7O (317.31): C, 60.56; H, 3.49; N, 30.90.
Found: C, 60.64; H, 3.55; N, 31.08.
Yield: 0.78 g (82%); yellow-orange solid; mp 295–297 °C (EtOH).
IR (KBr): 1463, 1477, 1595, 1618, 1670, 3165, 3283, 3368 cm–1.
N′-(3-Amino-1H-pyrrolo[3,4-b]quinoxalin-1-ylidene)isonicoti-
nohydrazide (4k)
Yield: 0.93 g (84%); yellow solid; mp 322 °C (DMF).
IR (KBr): 1514, 1681, 3192, 3340 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.83 (d, J = 4.4 Hz, 2 Hpy),
7.99–8.06 (m, 2 Hquin), 8.26 (d, J = 8 Hz, 1 Hquin), 8.32 (d, J = 8 Hz,
1 Hquin), 8.84, 8.98, and 9.14 (3 br s, 4 H, Hpy + NH2), 11.01 (br s, 1
H, NH).
1H NMR (400 MHz, DMSO-d6): δ = 8.00 (br s, 3 H, Hquin + NH),
8.24 (br s, 2 Hquin), 8.56 (br s, 1 H, NH), 9.02 and 9.08 (2 br s, 2 H,
NH2), 9.61 (br s, 1 H, NH).
13C NMR (100 MHz, DMSO-d6): δ = 130.5, 130.6, 131.8, 132.5,
141.5, 142.6, 148.4, 149.7, 150.5, 164.8, 177.8.
MS (CI): m/z (%) = 272 (100, [M + H+]).
Anal. Calcd for C11H9N7S (271.30): C, 48.70; H, 3.34; N, 36.14.
Found: C, 48.45; H, 3.41; N, 36.25.
13C NMR (100 MHz, CF3CO2D): δ = 122.0, 129.9, 132.0, 132.4,
134.0, 139.6, 140.5, 141.6, 147.8, 152.4, 153.3, 163.1, 167.8.
MS (CI): m/z (%) = 318 (100, [M + H+]).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
Anal. Calcd for C16H11N7O (317.31): C, 60.56; H, 3.49; N, 30.90.
Found: C, 60.71; H, 3.65; N, 30.99.
Compounds 5a,b, 6 and 7
References
Compounds 5a,b, 6, and 7 were obtained from the corresponding
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3375–3382

3382
O. V. Hordiyenko et al.
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