Reactions of cyanofurazans with β-dicarbonyl compounds

Article abstract of DOI:10.1023/A:1014075327382

In the presence of nickel acetylacetonate, β-dicarbonyl compounds readily add at the nitrite group of 4-R-3-cyanofurazans to form enaminofurazans. The adducts obtained from 4-amino-3-cyanofurazan underwent intramolecular cyclization on heating with AcOH in EtOH to give furazano[3,4-b]pyridine derivatives in high yields.

Full text of DOI:10.1023/A:1014075327382

1280
Russian Chemical Bulletin, International Edition, Vol. 50, No. 7, pp. 1280—1286, July, 2001
Reactions of cyanofurazans with β-dicarbonyl compounds
L. S. Vasil´ev, A. B. Sheremetev,« N. K. Khoa, Z. K. Dem´yanets, D. E. Dmitriev, and V. A. Dorokhov«
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. E-mail: sab@cacr.ioc.ac.ru
In the presence of nickel acetylacetonate, β-dicarbonyl compounds readily add at the
nitrile group of 4-R-3-cyanofurazans to form enaminofurazans. The adducts obtained from
4-amino-3-cyanofurazan underwent intramolecular cyclization on heating with AcOH in
EtOH to give furazano[3,4-b]pyridine derivatives in high yields.
Key words: furazans, cyanofurazans, β-diketones, β-oxo esters, enamines, furaza-
no[3,4-b]pyridines.
It is known that transition metal acetylacetonates
strated that furazan (1,2,5-oxadiazole) is among the
most active compounds in this series due to its pro-
nounced electron-withdrawing properties.
In the present work, we report the results of studies
on the reactions of cyanofurazans with β-dicarbonyl
compounds (for the preliminary communication, see
Ref. 10).
catalyze the addition of β-dicarbonyl compounds, which
contain the active methylene group, at the C≡N bond of
some activated nitriles, e.g., of trihalogenoacetonitri-
les,1—4 benzoylacetonitrile,5 and malononitrile.6,7 This
methodology also proved to be efficient in the synthesis
of polyfunctional compounds based on cyanohetero-
cycles. Thus acetylacetone adds to 2-cyanopyridine in
the presence of Ni(acac)2 at 110—120 °C to give adduct
1 (Scheme 1). Under the reaction conditions, the latter
decomposes to form 4-amino-4-(2-pyridyl)but-3-en-
2-one (2).8
Results and Discussion
We found that acetylacetone in the presence of a
catalytic amount of Ni(acac)2 added to 3-cyano-4-
ethoxyfurazan (3) even at room temperature to give
enaminodione 4 in 77% yield (Scheme 2).
Scheme 1
Scheme 2
Me
Me
Ni(acac)2, ∆
+
N
CN
O
O
EtO
CN
Ni(acac)2,
Me
Me
CH2Cl2, 20 °C
+
N
N
O
O
O
NH2
NH2
3
N
N
O
O
O
OEt
N
H
O
Me Me
Me
NH2
Me
N
1
2
Me
It was reasonable to expect that the use of more
reactive heterocyclic nitriles will allow one to perform
the reactions with compounds containing the reactive
methylene group under milder conditions, thus prevent-
ing decomposition of the primary adduct.
Based on the results of studies on the reactions of a
number of cyanoheterocycles with enols, the hetero-
cycles were arranged in the activity series according to
their ability to activate the C≡N bond.9 It was demon-
O
O
4
The 1H NMR spectrum (in DMSO-d6) of enamino-
dione 4 has a broadened signal for two Ac groups
(δ 2.24) and two broad signals of the amino group at
δ 8.8 (free NH) and δ 10.4 (NH bound to the O atom of
the acetyl group through an intramolecular hydrogen
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1220—1225, July, 2001.
1066-5285/01/5007-1280 $25.00 ©ꢀ2001 Plenum Publishing Corporation

Russ.Chem.Bull., Int.Ed., Vol. 50, No. 7, July, 2001
1281
Reactions of cyanofurazans
Table 1. Yields, melting points, the parameters of the IR and mass spectra, and the data from elemental analysis for enaminodiones
4 and 6 and furazano[3,4-b]pyridines 8, 10, and 12
–1
Com- Yield
M.p./°C
(solvent for
crystallization)
Found
Calculated
Molecular
formula
IR, ν/cm
Mass spectrum,
(%)
pound
(%)
m/z
(mol. weight)
C
H
N
4
77
86
83
104—105
(C6H6—heptane, 1 : 1) 50.21
50.25
5.45
5.48
4.81
4.80
4.51
4.44
17.38
17.56
26.08
26.66
20.53
20.58
C10H13N3O4
(239.23)
C8H10N4O3
(210.19)
C13H12N4O3
(272.26)
—
239 [M]+
6a
6b
∼150
45.43
45.71
57.12
57.35
3395, 3295, 3200 (NH2);
1650 (CO)
210 [M]+
208—210
(MeOH)
3405, 3320 (NH2);
3250, 3205 (CH);
1650 (CO); 1595 (C=N);
1510, 1410, 1265, 1030,
880, 750
254 [M+ – H2O]
6c
8a
8b
87
90
82
206—208
(MeOH)
64.48
64.67
4.25
4.22
16.89
16.76
C18H14N4O3
(334.33)
3435, 3320, 3240,
3170 (NH, CH);
—
1640 (CO); 1600, 1570
(C=N); 1470, 1320,
1280, 1000, 970, 900
3450, 3350, 3300,
3240 (NH); 2230 (C≡N);
1680, 1650, 1620,
1580 (C=N); 1475, 1420,
1140, 1100, 875, 850
3395, 3310, 3225,
3060 (NH, CH); 1665
(CO); 1645 (C=N);
1595, 1540, 1505,
1495, 1380, 1335, 1260,
1030, 960, 890
197—198
49.95
50.00
4.23
4.20
29.32
29.15
C8H8N4O2
(192.18)
192 [M]+,
162 [M+ – NO]
257—258
(MeOH)
61.23
61.41
3.65
3.96
22.34
22.04
C13H10N4O2
(254.25)
254 [M]+,
224 [M+ – NO]
8c
88
176—178
68.41
68.35
3.95
3.82
17.59
17.71
C18H12N4O2
(316.32)
3405, 3330, 3245,
3165 (NH, CH); 1640
(CO); 1595 (C=N);
1450, 1275, 920, 690
—
316 [M]+,
286 [M+ – NO]
10a
10b
90
83
179—180
(Ñ6Í6)
168—170
(MeOH)
48.94
48.65
58.96
59.15
4.70
4.54
4.13
4.25
25.12
25.21
19.61
19.71
C9H10N4O3
(222.20)
C14H12N4O3
(284.27)
—
3410, 3350, 3260 (NH2);
3000 (CH); 1700 (CO);
1640 (C=N); 1600,
1550, 1290
3415, 3210, 3010, 2960
(NH, CH); 2600—2300,
1790, 1670, 1640,
1450, 1395
284 [M]+
12
67
238—239
(MeOH)
58.06
57.98
5.14
5.21
24.46
24.14
C11H12N4O2
(232.24)
232 [M]+
bond) along with signals of the EtO group (δ 1.35 and
4.35). The integral intensity of the signals is in complete
agreement with the structure of 4. The mass spectrum of
compound 4 has a molecular ion peak at m/z = 239
(Table 1).
4-Amino-3-cyanofurazan (5) is a more promising
furazan derivative for the use in the analogous reaction
because its structure is favorable for annelation with the
furazan ring of the second heterocycle.
Actually, as in the case of nitrile 3, the addition of
acetylacetone, benzoylacetone, or dibenzoylmethane to
cyanofurazan 5 proceeded under mild conditions
(CH2Cl2, 20 °C, catalytic amount of Ni(acac)2) to form
the expected enaminodiones 6a—c in 83—87% yields
(Scheme 3). As compounds 6a—c were formed, they
precipitated, and hence no additional purification was
required.
The reaction is characterized by high regioselectivity.
Thus an alternative condensation involving the amino
group to give enamines 7a—c (analogous to that gener-
ally observed in the reactions of aminofurazans with
various carbonyl compounds11) did nor occur under
these conditions.
Although the time of conversion of the starting
compounds in the reaction performed in boiling CH2Cl2
is shorter, the resulting enaminodiones 6a—c under-
went partial cyclization to the corresponding furaza-
no[3,4-b]pyridines (8a—c). It should be noted that the
reactions of nitrile 5 with β-diketones can also be
promoted by sodium acetate in aqueous methanol. How-

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Russ.Chem.Bull., Int.Ed., Vol. 50, No. 7, July, 2001
Vasil´ev et al.
Scheme 3
ever, prolonged heating at 50—60 °C was required for
complete conversion of the reactants. The reaction was
accompanied by the formation of a number of by-
products, which substantially hampered isolation and
purification of enaminodiones 6a—c.
R1
NH
O
CN
Compounds 6a—c were obtained as white powders
readily soluble in DMSO, less soluble in acetone and
alcohol, and insoluble in hexane. Their structures were
confirmed by spectral methods (see Tables 1 and 2).
Thus the mass spectra have molecular ion peaks. The
1H NMR spectra are in complete agreement with the
proposed structures. For example, the spectrum of com-
pound 6a has a broad signal of two MeCO groups at
δ 2.12, the signal of the amino group bound to the
furazan ring at δ 6.3, and two low-field broad signals at
δ 7.4 (free NH group) and 10.42 (H-bound NH group).
It thus follows that the amino group of the enaminodione
fragment is involved in intramolecular hydrogen bonding.
In the 13C NMR spectra (see Table 2), three most
common and characteristic signals can be noted. Thus
1
2
N
N
R
R
O
R2
,
O
O
H2N
N
CN
Ni(acac)2,
CH2Cl2
7a—c
N
R2
R1
O
5
O
O
H2N
NH2
N
N
O
6a—c
R1 = R2 = Me (a), R1 = Me, R2 = Ph (b); R1 = R2 = Ph (c)
Table 2. Chemical shifts (δ) in the 1H and 13C NMR spectra of enaminodiones 4, 6a—c, and 9a (DMSO-d6)
O
5
R2
R3
H2N
3
4
R1
1
2
6
O
N
N
O
Com-
pound
R1
R2
R3
δ
1H
13C
C(1) C(2) C(3) C(4) C(5)
C(6)
—
4
OEt
Me
Me
1.35 (t, 3 Í, MeCH2);
2.24 (s, 6 H, 2 As);
4.35 (q, 2 H, OCH2);
8.80 (br.s, 1 Í, NH);
10.42 (br.s, 1 Í, NH)
2.12 (br.s, 6 Í, 2 As);
6.30 (s, 2 H, NH2):
8.74 (br.s, 1 Í, NH);
10.40 (br.s, 1 Í, NH)
2.16 (s, 3 H, Me);
—
—
—
—
—
6a*
NH2 Me
NH2 Me
Me
Ph
156.8 146.1 150.1 115.7 197.5
155.2 144.5 151.7 112.9 196.3
197.5
195.6
6b**
6.39 (s, 2 H, NH2);
7.30—7.60 (m, 5 H, Ph);
8.79 (br.s, 1 Í, NH);
10.75 (br.s, 1 Í, NH)
6.25 (s, 2 H, NH2);
7.10—7.55 (m, 10 H, Ph);
9.2 (br.s, 1 Í, NH);
10.2 (br.s, 1 Í, NH)
0.95 (t, 3 H, MeCH2);
2.30 (s, 3 H, Me);
6s
NH2 Ph
NH2 Me
Ph
155.4 144.9 152.7 111.2 194.5
194.5
—
9a
OEt
—
—
—
—
—
3.87 (q, 2 H, OCH2);
6.19 (s, 2 H, NH2);
8.95 (br.s, 1 Í, NH);
10.76 (br.s, 1 Í, NH)
* The signal of the substituent R2 in the 13C NMR spectrum is observed at δ 31.2.
** The signal of the substituent R2 in the 13C NMR spectrum is observed at δ 29.9.

Russ.Chem.Bull., Int.Ed., Vol. 50, No. 7, July, 2001
1283
Reactions of cyanofurazans
Table 3. Nuclear Overhauser effect (NOE) for compound 6b
acid in ethanol gave rise directly to the cyclization
products. In this case, the final furazano[3,4-b]pyridines
were obtained in substantially higher yields than in the
two-stage procedure.
Enaminodiones 6a and 6c prepared from symmetri-
cal β-diketones can produce the only condensation
products, viz., 8a and 8c, respectively.
Irradiated
NOE on protons (%)
signal, δ
Me,
m-Ph,
NH2,
NH2,
NH2,
δ 2.16
δ 7.80
δ 6.39
δ 8.79 δ 10.75
CH3, 2.16
NH2, 6.39
NH2, 8.79
NH2, 10.75
—
—
—
—
+1.1
+1.5
—
—
—
–21
–21
—
–23
—
—
–23
—
—
—
—
Scheme 4
R2
R1
the chemical shift of the C atom of the furazan ring
bound to the amino group is observed at δ 154.9—155.4.
The signals for another C atom of the ring bound to
the enamino group are observed at higher field (at
δ 141.8—144.9). The C atom of the enamine frag-
ment bound to the amino group gives a signal at
δ 151.7—152.7.
4
3
R2
3a
7a
N
5
O
O
N
AcOH/EtOH
2O
H2N
6
R1
NH2
N
1
7
N
N
NH2
O
O
6a—c
8a—c
The IR spectrum (in KBr) of compound 6a has a
band of the carbonyl group (1650 cm–1) along with
three bands at 3395, 3295, and 3200 cm–1, which
should be assigned to vibrations of NH (the free group
and the group involved in intramolecular hydrogen bond-
Enaminodione 6b also gave the only product 8b due
apparently to the E configuration of the starting
enaminodione 6b. In the 13C NMR spectrum of
furazano[3,4-b]pyridine 8b measured without suppres-
sion of the H—C coupling, the signal for the C atom of
the carbonyl group is observed as a quartet at δ 201,
which is indicative of the presence of the MeCO group.
Nickel acetylacetonate also efficiently catalyzed the
reactions of nitrile 5 with β-oxo esters. Thus the reac-
tion with ethyl acetoacetate in the presence of Ni(acac)2
proceeded rapidly in CH2Cl2 (Scheme 5).
–1
ing). No absorption at 2100—2200 cm characteristic
of the nitrile group was observed.
Compound 6b contains nonequivalent substituents
at the double bond (Ac and Bz). The configuration of
this enaminodione was established by measuring the
nuclear Overhauser effect (NOE) in the 1H NMR spec-
tra (Table 3).
It can be seen from Table 3
that NOE on the protons of the
benzene ring (1.5%), but not
on the protons of the methyl
group, was observed upon pre-
irradiation of the protons of the
amino group directly bound to
the furazan ring (δ 6.39), which
corresponds to the E configura-
tion of compound 6b.
Ph Me
O
O
Scheme 5
H
H2N
N
H2N
CN
OEt
R
H
N
N
O
O
O
N
N
Ni(acac)2,
CH2Cl2
O
--6b
5
The observed small values of NOE for the protons of
the benzoyl group may be due to relaxation at the
benzene ring. The large negative values of NOE be-
tween two amino groups are indicative of intense intra-
and intermolecular exchange of the NH protons. The
presence of the hydrogen bond between one of the NH
protons of the enamine fragment and the acetyl group
leads to the nonequivalence of the protons of this amino
group.
We found that heating of the resulting enaminodiones
in ethanol in the presence of acetic acid afforded the
corresponding furazano[3.4-b]pyridines (8a—c) in high
yields (Scheme 4). It should be noted that the isolation
of enaminodiones 6a—c in individual form is not neces-
sary for the synthesis of annelated derivatives 8a—c.
Condensation of nitrile 5 with β-dicarbonyl compounds
followed by heating of the reaction mixtures with acetic
R
OEt
O
O
N
R
N
N
H2N
O
+
NH2
CO2Et
N
N
NH2
O
9a,b
10a,b
R = Me (a), Ph (b)
In this case, a substantial portion of the resulting
enaminodione 9a underwent intramolecular cyclo-
condensation even at room temperature to give ethyl
furazano[3,4-b]pyridine-3-carboxylate 10a. After 10 h
(the time required for complete consumption of the

1284
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 7, July, 2001
Vasil´ev et al.
starting nitrile 5), the reaction mixture contained prod-
ucts 9a and 10a in approximately equal amounts. Pure
enamino ester 9a was isolated by column chromato-
graphy on silica gel.
Analogously, the reaction of nitrile 5 with ethyl
benzoylacetate afforded a mixture of enamino ester 9b
and bicyclic compound 10b.
Intramolecular cyclization of enamino esters 9a and
9b also proceeded regioselectively. Heating of these
compounds (generally, of the re-
Furazano[3,4-b]pyridines synthesized in the present
study were characterized by the data from mass spec-
trometry, IR spectroscopy, and elemental analysis (see
Table 1) and by 1H and 13C NMR spectroscopy
(Table 4). Single crystals of compound 8a were studied
by X-ray diffraction analysis.10
All signals in the 13C NMR spectra of furaza-
no[3,4-b]pyridines (see Table 4) were unambiguously
assigned. Thus the C atoms of the furazan rings (C(3a))
bound to the N atom of the pyridine ring give signals at
δ 157.9—159.8, which are no different from that observed
in the spectrum of unsubstituted furazano[3,4-b]pyridine
(cf. lit.13: δ 158.4). The signals for the other C atoms of
the furazan rings (C(7a)) are observed at higher field
and are also located in a narrow range (δ 139.5—140.0).
The presence of substituents in the pyridine moiety of
the molecule leads to a substantial change in the corre-
sponding chemical shifts (by 10—20 ppm) compared to
those observed in the spectrum of the parent compound
of this class of bicycles.
action mixture containing com-
R
pounds 9 and 10) in the presence
O
O
of acetic acid resulted in conden-
sation of the acyl carbonyl group
with the amino group in the furazan
ring to form esters 10a and 10b,
respectively. No products, which
might be formed in the reaction
involving the ethoxycarbonyl group,
(such as 11) were detected.
HN
NH2
N
N
O
11
Catalysis of the addition of acyclic β-dicarbonyl
compounds to reagents containing the C≡N bond is
based on the intermediate formation of chelate com-
plexes of the ketoenol type. Hence, cyclic β-diketones
which cannot form such chelates do not react with
activated nitriles in the presence of catalytic amounts of
Ni(acac)2. However, it was shown12 that, for example,
the addition of cyclohexane-1,3-dione or dimedone to
cyanamides can be performed in the presence of an
equimolar amount of nickel acetate Ni(OAc)2. In this
case, the corresponding nickel enolate was apparently
formed as the reaction intermediate. In the study of the
reaction of cyanofurazan 5 with dimedone, we used an
analogous approach. Actually, nitrile 5 rapidly disap-
peared (according to the TLC data) upon refluxing with
dimedone and Ni(OAc)2 (taken in a ratio of 2 : 2 : 1) in
DMF. After treatment with dilute HCl, tricylcic com-
pound 12 was isolated in 67% yield (Scheme 6).
In conclusion, it should be noted that the results of
our study demonstrated the efficiency of the catalytic
addition of β-dicarbonyl compounds to cyanofurazans
in the synthesis of polyfunctional furazan derivatives.
This method provided the basis for the development of a
convenient procedure for the preparation of furaza-
no[3,4-b]pyridine derivatives. Enaminodiones under
study are convenient starting compounds for their con-
versions into various non-cyclic and annelated furazan
derivatives. Synthetic possibilities of the resulting
enaminodiones and furazano[3,4-b]pyridines will be de-
scribed in more detail elsewhere.
Experimental
The IR spectra were measured on a Perkin—Elmer 577
spectrophotometer in KBr pellets. The mass spectra (EI) were
obtained on a Varian MAT-311A instrument (70 eV). The 1H
and 13C NMR spectra were recorded on a Bruker AM-300
instrument (300 and 75 MHz, respectively) in DMSO-d6. The
assignment of the signals in the 13C NMR spectra were made
based on the double heteronuclear resonance. The nuclear
Overhauser effect was measured using the NOEDIF program
included in the software of the spectrometer. The purities of the
compounds were monitored by TLC on Silufol UV-254 plates.
As we mentioned in the preliminary communica-
tion,10 furazano[3,4-b]pyridines have been previously
unknown. Only N-oxides of this heterocyclic system
have been described. The synthesis of unsubstituted
furazano[3,4-b]pyridine has been reported only re-
cently.13 The results of investigations on derivatives of
this heterocyclic system were surveyed in the review.14
Scheme 6
O
NH2
N
O
Me
Me
Ni(OAc)2
H2N
CN
4
O
3
NH
N
Me
Me
2 O
3a
9a
N
N
N
5
8
+
4a
8a
6
7
H
2O
N
N
N
O
O
N
1
HN
O
O
9
Ni
NH2
O
5
)
NH2
O
2
12

Russ.Chem.Bull., Int.Ed., Vol. 50, No. 7, July, 2001
1285
Reactions of cyanofurazans
Table 4. Chemical shifts (δ) in the 1H and 13C NMR spectra of furazano[3,4-b]pyridines 8a—c and 10a,b (DMSO-d6)
Com-
pound
δ
1H
13C
C(3a) C(7a) C(7) C(6) C(5) C=O
Other C atoms
8a
2.51 (s, 3 H, Me);
158.0 139.7 142.2 113.7 167.6 202.2 26.2 (Me); 31.6 (COMe)
2.58 (s, 3 H, Me);
8.23 (br.s, 2 H, NH2)
3.34 (s, 3 H, Me);
7.50—7.60 (m, 5 H, Ph);
8.79 (br.s, 2 H, NH2)
8b
157.9 139.5 144.3 111.9 169.1 200.2 31.6 (Me); 140.8 (i), 130.2 (p),
128.62, 128.56 (m, o) (Ph)
8s
7.18—7.56 (m, 10 H, 2 Ph); 159.8 140.0 144.6 110.3 168.5 195.7 138.5 (i), 132.8 (p), 128.0, 128.2 (m, o),
8.30 (br.s, 2 H, NH2)
(COPh); 140.2 (i), 129.5 (p), 128.8,
129.0 (m, o) (Ph)
10a
1.42 (t, 3 H, MeCH2);
2.65 (s, 3 H, Me);
157.9 139.7 145.9 102.1 169.7 166.7 13.9 (CH2Me); 27.8 (Me); 61.0 (CH2)
4.40 (q, 2 H, OCH2);
8.60 (br.s, 2 H, NH2)
0.74 (t, 3 H, MeCH2);
3.92 (q, 2H, OCH2);
7.40—7.50 (m, 5 H, Ph);
8.62 (br.s, 2 H, NH2)
10b
158.4 139.6 145.8 102.6 169.2 166.8 13.1 (Me); 60.9 (CH2); 141.5 (i),
129.1 (p), 127.96, 127.67 (m, o) (Ph)
3-Cyano-4-ethoxyfurazan15 and 4-amino-3-cyanofurazan16
were prepared according to procedures reported previously.
The yields, the melting points, the data from elemental
analysis, and the spectral characteristics of the compounds
synthesized are given in Tables 1, 2, and 4.
cyanofurazan 5 (0.11 g, 1 mmol), and Ni(acac)2 (0.012 g,
0.046 mmol) in dry CH2Cl2 (3 mL) was stirred at ∼20 °C for
10 h. The solvent was evaporated in vacuo and the residue was
chromatographed on a column with SiO2 (CHCl3 as the elu-
ent). Product 9a was obtained in a yield of 0.07 g.
3-Acetyl-4-amino-4-(4-ethoxyfurazan-3-yl)but-3-en-2-one
A mixture of cyanofurazan 3 (0.59 g, 4.2 mmol),
7-Amino-6-ethoxycarbonyl-5-methylfurazano[3,4-b]pyridine
(10a). A mixture of cyanofurazan 5 (0.11 g, 1 mmol), ethyl
acetoacetate (0.2 g, 1.5 mmol), and Ni(acac)2 (0.012 g,
0.046 mmol) in dry CH2Cl2 (10 mL) was refluxed for 3 h. Then
three drops of acetic acid were added. The mixture was refluxed
for 1 h and concentrated in vacuo to dryness. The residue was
recrystallized from a 20 : 1 C6H6—MeOH mixture and product
10a was obtained in a yield of 0.18 g.
(4).
acetylacetone (2 mL), and Ni(acac)2 (0.11 g, 0.42 mmol) in dry
CH2Cl2 (7 mL) was stirred for 5 h. The solvent was distilled off
in vacuo and the residue was purified by column chromatogra-
phy on SiO2 (benzene—hexane as the eluent). Product 4 was
obtained in a yield of 0.78 g.
3-Acetyl-4-amino-4-(4-aminofurazan-3-yl)but-3-en-2-one
(1.1 g, 10 mmol),
(6a).
A
mixture of cyanofurazan
5
7-Amino-6-ethoxycarbonyl-5-phenylfurazano[3,4-b]pyridine
(10b) was prepared analogously from ethyl benzoylacetate.
9-Amino-6,6-dimethyl-5,6,7,8-tetrahydrofuraza-
no[3.4-b]quinolin-8-one (12). A mixture of cyanofurazan 5
(0.44 g, 4 mmol), dimedone (0.56 g, 4 mmol), and nickel
acetate (0.36 g, 2 mmol) in DMF (10 mL) was refluxed for 2 h.
The solvent was distilled off in vacuo. A solution of 8.6 M HCl
in ethanol (0.46 mL) and MeOH (4 mL) were added to the
residue. The reaction mixture was stirred for 10 min and then
water (5 mL) was added. The precipitate that formed was
filtered off and dried in a desiccator over P2O5. The resulting
dark powder (0.61 g) was purified on a column with SiO2
(CHCl3 as the eluent). The product was obtained as a pale-gray
powder in a yield of 0.46 g. 1H NMR (CDCl3), δ: 1.12 (s, 6 H,
2 Me); 2.58 and 2.99 (both s, 2 H each, CH2); 6.75 and 10.25
(both br.s, 1 H each, NH). 13C NMR (DMSO-d6), δ: 27.6 and
31.1 (both Me); 48.1 (C(5)); 51.9 (C(7)); 95.5 (C(6)); 104.5
(C(8a)); 140.1 (C(9a)); 147.2 (C(9)); 158.2 (C(3a)); 172.5
(C(4a)); 199.2 (C(8)).
acetylacetone (1.2 g, 1.25 mL, 12 mmol), and Ni(acac)2 (0.026 g,
0.1 mmol) in dry CH2Cl2 (40 mL) was stirred at ∼20 °C for 6 h,
kept for 12 h, and then refluxed for 3 h. The precipitate that
formed was filtered off and washed with CH2Cl2 to obtain a
product in a yield of 1.82 g. The product melted at ∼150 °C and
immediately crystallized to form a yellow compound with a
higher melting point.
4-Amino-4-(4-aminofurazan-3-yl)-3-benzoylbut-3(E)-en-2-
one (6b) was prepared analogously starting from benzoylacetone.
The reaction was performed at ∼20 °C for 36 h.
3-Amino-3-(4-aminofurazan-3-yl)-2-benzoyl-1-phenylprop-
2-en-1-one (6c) was prepared analogously starting from diben-
zoylmethane. The reaction at ∼20 °C was completed in 50 h.
6-Acetyl-7-amino-5-methylfurazano[3,4-b]pyridine (8a). A
solution of enaminodione 6a (0.5 g, 2.4 mmol) in EtOH
(5 mL) with five drops of AcOH was refluxed for 2 h. The
precipitate that formed was filtered and product 8a was ob-
tained in a yield of 0.41 g.
6-Acetyl-7-amino-5-phenylfurazano[3,4-b]pyridine (8b) was
prepared analogously from enaminodione 6b upon refluxing for 5 h.
7-Amino-6-benzoyl-5-phenylfurazano[3,4-b]pyridine (8c)
was prepared analogously from enaminodione 6c upon reflux-
ing for 10 h.
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Received December 20, 2000