A highly efficient and reusable catalyst for the synthesis of 4H-benzo[b]pyran derivatives

Article abstract of DOI:10.1515/hc-2019-0025

A series of substituted 4H-pyrans derivatives were synthesized by a one-pot, multi-component reaction of aromatic aldehydes, malononitrile, and pyrazolone derivatives or active methylene carbonyl compounds such as dimedone, in the presence of 1,3-dimethyl

Full text of DOI:10.1515/hc-2019-0025

Heterocycl. Commun. 2019; 25: 167–179
Research Article
Open Access
Mohamed Abdenour Redouane, Naima Khiri-Meribout*, Saida Benzerka and
A[DbdeMlmIamdjiddD-ebDacMheP]: A highly efficient and reusable
catalyst for the synthesis of 4H-benzo[b]pyran
derivatives
https://doi.org/10.1515/hc-2019-0025
4H-pyran derivatives represent an important class of
oxygen-containing heterocycles. They are often employed
as cosmetics, pigments [6], and potential biodegradable
agrochemicals [7] and exhibit a wide range of biological
activities [8-17]. Moreover, they possess important medi-
cinal properties such as antimicrobial, antibacterial,
anticancer, anti-tubercular, anti-coagulant, anti-allergic,
antibiotic, hypolipidemic, and immunomodulating acti-
vities [18-25]. In addition, they can be used as cognitive
enhancers, for the treatment of neurodegenerative disea-
ses like Alzheimer’s disease, amyotrophic lateral scle-
rosis, Huntington’s disease, Parkinson’s disease, AIDS
associated dementia and Down’s syndrome, as well as for
the treatment of schizophrenia and myoclonus [26].
Realizing the importance of 4H‐pyran derivatives,
various synthetic approaches have been developed with
the aim of obtaining more biologically potent heterocyc-
lic systems using different catalysts such as magnesium
oxide [27], silica‐bonded 1,4‐diazabicyclo[2.2.2]octane
[28], silica nanoparticles [29], electro‐generated base [30],
baker’s yeast [31], and amino‐functionalized ionic liquid
[32]. Other synthetic methods have included the use of
microwaves [33], ultrasonic radiation [34], and utilizing
additives like hexadecyltrimethylammonium bromide
[35], triethylbenzylammonium chloride [36], other alkyl-
ammonium salts [37], 4‐dodecylbenzenesulfonic acid [38],
morpholine triflate [39], Trichloroacetic acid [40], imida-
zole [41], lemon juice [42], DABCO [43], (S)‐proline [44], tri-
phenylphosphine [45], PEG-400 [46], β-cyclodextrin [47],
[MNP-PIm-SO3H]Cl [48], uncapped SnO2 quantum dots
(QDs) [49], Fe3-xTixO4@SO3H magnetic nanoparticles [50],
nano-structured diphosphate (Na2CaP2O7) [51], γ-alumina
[52], silica coated magnetic NiFe2O4 nanoparticles suppor-
ted H3PW12O40 (NFSPWA) [53] and cerium ammonium
nitrate (CAN) [54].
Received April 28, 2019; accepted September 15, 2019.
Abstract: A series of substituted 4H-pyrans derivatives
were synthesized by a one-pot, multi-component reac-
tion of aromatic aldehydes, malononitrile, and pyrazolone
derivatives or active methylene carbonyl compounds such
as dimedone, in the presence of 1,3-dimethyl imidazo-
lium dimethyl phosphate [DMImd-DMP] as a catalyst in
aqueous ethanol. Recyclability of the catalyst, high yields,
simple product isolation and high atom economy are the
noteworthy aspects of this protocol.
Keywords: multicomponent reaction, one-pot synthesis,
pyrano[2,3-c]pyrazoles, tetrahydrobenzo[b]pyrans, ionic
liquids, [DMImd-DMP].
Introduction
Multicomponent reactions (MCRs) are one of the most
important reactions in organic and medicinal chemistry
because they are widely used for synthesis of diverse and
complex organic molecules [1-3]. They are known to be
selective, have effective atom economic, and are gene-
rally time saving and easy to perform. As such, MCRs have
attracted much attention from both academia and the
pharmaceutical industry [4,5].
* Corresponding author: Naima Khiri-Meribout, Laboratory
of Synthesis of Molecules with Biological Interest, Mentouri-
Constantine 1 University, 25000 Constantine, Algeria,
e-mail: naima.khiri@umc.edu.dz
Mohamed Abdenour Redouane, Saida Benzerka and
Abdelmadjid Debache, Laboratory of Synthesis of Molecules
with Biological Interest, Mentouri-Constantine 1 University,
25000 Constantine, Algeria
However, these methods were shown to have limita-
tions and proved ineffective, such as low yields and dif-
ficult work-up procedures. Bandgar and coworkers [55]
Open Access. © 2019 Redouane et al., published by De Gruyter.ꢀ
Attribution alone 4.0 License.
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M. A. Redouane et al.: [DMImd-DMP]: A highly efficient and reusable catalyst
Scheme 1ꢂSynthesis of 4H-pyran derivatives in the presence of 1,3-dimethyl imidazolium dimethyl phosphate [DMImd-DMP].
Scheme 2ꢂSynthesis of 1,3-dimethyl imidazolium dimethyl phosphate [DMImd-DMP].
reported the synthesis of tetrahydrobenzo[b]pyrans in Results and discussion
good yield without the use of a catalyst, although pro-
longed reaction times were required.
The first step in the execution of this process was the syn-
In recent years, ionic liquids (ILs) have become a thesis of [DMImd-DMP]. The catalyst was prepared from
powerful alternative to conventional molecular organic the quaternization of N-methylimidazole with trimethyl-
solvents due to their favourable properties, such as unde- phosphate as shown in Scheme 2. The catalyst structure
tectable vapor pressure, and the ability to dissolve many was investigated by NMR spectroscopy. The pure N,N-
organic and inorganic substances [56]. Furthermore, the methylimidazolium dimethylphosphate shows charac-
ILs are readily recycled and tunable to specifics chemical teristic peaks at 3.85 ppm and 4.12 ppm corresponding
tasks [57]. Imidazolium-based ILs have proved their cata- to (2 × OCH3) and (2 × N-CH3) groups, respectively. These
lytic activity and have attracted considerable attention results prove that the methyl, provided from trimethyl-
from the scientific community, due to the ease of prepara- phosphate, was successfully added to N-methylimidazole
tion from readily available and inexpensive starting mate- to give 1,3-dimethyl imidazolium dimethyl phosphate
rials [57j-k].
In this paper, we would like to report an efficient
[DMImd-DMP].
In order to find the best reaction conditions for the
process for the synthesis of 4H-pyran derivatives by synthesis of 4H-pyran derivatives, our introductory
employing 1,3-dimethyl imidazolium dimethyl phosphate explorations focused on the study of the efficacy of this
[DMImd-DMP] as an efficient and recyclable catalyst. We catalyst.
examined a wide variety of benzaldehydes with various
To establish the feasibility of the strategy and opti-
substituents to establish the catalytic importance of this mize the reaction conditions, the condensation of benz-
catalyst for this reaction (Scheme 1).
aldehyde (1a) (1 mmol) with malononitrile (2) (1 mmol)
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Scheme 3ꢂOne-pot three-component reaction of dimedone (3a), different aldehydes (1a-n), and malononitrile (2) catalyzed by [DMImd-DMP].
Scheme 4ꢂOne-pot three-component reaction different aldehydes (1), malononitrile (2) and 3-methyl-1-phenyl-2-pyrazolin-5-one (3b)/
5-methyl-2,4-dihydro-3H-pyrazol-3-one (3c) catalyzed by [DMImd-DMP].
and 5,5-dimethylcyclohexane-1,3-dione (3a) (1 mmol) Table 1ꢂ[DMImd-DMP]-catalyzed reaction of benzaldehyde, malono-
nitrile, and 5,5-dimethylcyclohexane-1,3-dione in different solventsa
in the presence of 10 mol% of [DMImd-DMP] was selec-
ted as a reaction model to produce 4H-benzo[b]pyran
(4a) (Scheme 3). Also, benzaldehyde (1a) (1 mmol) with
malononitrile (2) (1 mmol) and 3-methyl-1-phenyl-2-pyra-
zolin-5-one (3b) (1 mmol) in the presence of 10 mol% of
[DMImd-DMP] as a second reaction model for the synthe-
sis of pyrano[2,3-c]pyrazole derivatives (5) and (6), respec-
tively (Scheme 4).
Entry
Solvent
Catalyst
(mol%)
Time
(h)
Yield
(%)b
1
2
3
4
5
6
7
8
9
Solvent Free
10
10
10
10
10
10
10
10
10
1.5
3.5
2
78
59
CH3CN
H2O
68
EtOH
2.5
3.5
24
76
The choice of a solvent is a crucial factor for MCRs.
So, firstly we looked into the appropriate solvent for this
reaction, especially in terms of starting materials solubi-
lity. We then tested the reaction in different solvents such
as H2O, EtOH, CH3CN, THF, and DMF in the presence of
10 mol% of [DMImd-DMP] as a catalyst. Furthermore, the
reaction was carried out under solvent-free conditions
(Table 1, Entry 1). However, aqueous ethanol (1:1) turned to
be the best solvent for this reaction. The obtained results
are given in Table 1. We obtained the best results at reflux
(Table 1, Entry 7); hence all the reactions were performed
at reflux in solvent.
THF
89
DMF
Trace
91
47
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)c
Aqueous EtOH (1:1)d
1.5
1.5
1.5
77
a Reaction conditions: benzaldehyde (1 mmol), malononitrile
(1 mmol), 5,5-dimethylcyclohexane-1,3-dione (1 mmol), [DMImd-
DMP] (22 mg), and solvent (5 mL).
b Isolated yields.
c Room temperature.
d 50 °C.
The temperature played an important role, there was
a formation of trace amounts of product formed which obtained when the reaction was carried out in aqueous ethanol
longer reaction times. As the temperature increased, (1:1) at reflux (Table 1, entry 7).
from room temperature to reflux in solvent, the yields
Apart from the solvent, the efficiency of MCRs is
were found to increase while the reaction time decreased mainly affected by the amount of catalyst. Next, to
(Table 1, entries 8 and 9). Higher yields and shorter reac- obtain the best conditions we carried out the above con-
tion times to synthesis 4H-benzopyrans model reaction were densation, under the optimized conditions, with various
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M. A. Redouane et al.: [DMImd-DMP]: A highly efficient and reusable catalyst
Table 2ꢂOptimization of amount of catalyst for synthesis of
4H-benzopyrane.a
Table 3ꢂOptimization of reaction conditions for the synthesis of
pyranopyrazole.a
Entry
Catalyst (mol%)
Time (h)
Yield (%)b
Entry
Solvent
Catalyst
(mol%)
Time
Yield
(%)b
(h or min)
1
2
3
4
5
5
1.5
1.5
1.5
1.5
1.5
75
91
84
74
59
10
15
20
30
1
2
Solvent Free
CH3CN
10
10
3 h
24 h
68
71
3
H2O
10
10
10
10
10
5
24 h
3 h
Trace
36
69
23
84
88
77
73
65
16
4
EtOH
a Reaction conditions: benzaldehyde (1 mmol), malononitrile
(1 mmol), dimedone (1 mmol) and catalyst [DMImd-DMP] in 5 mL
solvent H2O/EtOH (1:1) at reflux.
5
THF
3 h
6
DMF
5 h
b Isolated yield.
7
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)
Aqueous EtOH (1:1)
80 min
45 min
90 min
2 h
8
amountsofcatalystincreasingfrom5to30mol%(Table2).
After reviewing the results, it was found that an amount
of 10 mol% was sufficient to provide a best yield.
However, the use of 5 mol % of [DMImd-DMP] or incre-
asing it to more than 10%, (Tables 2, entries 1-5) has no
positive effect even on yield and reaction time. Thus, the
optimal conditions for the preparation of 4H-benzo-[b]
pyrans catalyzed by [DMImd-DMP] are: reflux in aqueous
ethanol (1:1) and 10 mol% of catalyst. The same process
was followed to optimize the best conditions for the
pyranopyrazole 5 model reaction. As shown in Table 3,
when the reaction was carried in the presence of 10 mol%
of catalyst, in various solvents, desired product (5a) is
obtained with yields ranging between 23 and 84 %, in
9
15
20
30
-
10
11
12
2 h
3 h
13
14
Aqueous EtOH (1:1)c
Aqueous EtOH (1:1)d
5
5
45 min
45 min
58
71
a Reaction conditions: benzaldehyde (1 mmol), malononitrile
(1 mmol), pyrazolone derivative (1 mmol), catalyst [DMImd-DMP] in
5 mL solvent at reflux.
b Isolated yield.
c room temperature.
d 50 °C.
which the shortest reaction time was 80 min (Table 3, 4H-pyran derivatives without by-products (Table 4, entries
entries 1-7). However, the reaction in aqueous ethanol 12, 20 and 21).
(1:1) at reflux gave a better result with a yield of 88 % in
In view of green chemistry, reuse of the catalyst is
presence of 5 mol% of our catalyst within 45 min (Table 3, highly preferable. The reusability of the catalyst was
entry 8).
studied on the synthesis of compounds 4a and 4h. After
To probe the efficiency and the scope of our method, separating the products, the IL catalyst was easily reco-
a broad range of structurally diverse aldehydes (1) were vered and recycled by removing the filtrate. Products 4a
condensed
with
5,5-dimethylcyclohexane-1,3-dione and 4h were obtained with excellent yields in consecutive
(3a)/3-methyl-1-phenyl-2-pyrazolin-5-one(3b)/5-methyl-2,4- 1 to 7 runs, respectively, which indicated that the catalyst
dihydro-3H-pyrazol-3-one (3c) and malononitrile (2) to could be reused for at least 6 runs without losing its acti-
furnish the corresponding 4H-pyran derivatives in high vity (Figure 1).
yields and in relatively short reaction times (Scheme 1).
The role of [DMImd-DMP] in the synthesis of
The corresponding results are given in Table 4. For all the 4H-pyrans (4-6) can be explained by the strict sequence
entries, aqueous ethanol (1:1) was used as solvent and the of the reactions shown in Scheme 5. Based on this mecha-
reaction was conducted at reflux. In all cases, the con- nism, [DMImd-DMP] is an effective catalyst for the forma-
version was completed within 20-120 min with good to tion of olefin (7), which is readily prepared in-situ from
excellent yields of desired products, without forming any the Knoevenagel condensation of aldehyde (1) with highly
by-products. We found that the reaction proceeded effici- active CH-acidic malononitrile (2). Carbonyl compound
ently employing either electron-releasing or electron- (3), in the presence of [DMImd-DMP], subsequently con-
withdrawing substituents on the aldehyde’s aryl ring. verts to its corresponding enolate form (8), and adds to
Moreover, heteroaromatic aldehydes such as thiophene- the unsaturated nitrile (7) by Michael reaction to produce
2-carbaldehyde and indole-3-carbaldehyde, were applied intermediate (9), and enolate oxygen nucleophilically
successfully in the reaction to provide the corresponding attacks nitrile group (Thorpe-Ziegler type reaction).
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Table 4ꢂSynthesis of 4H-pyran derivatives in the presence of [DMImd-DMP] under Optimized conditions.a
Entry
R
Substrate
Product
Time
(min)
Yield b
(%)
Melting point (°C)
Found Reported
1
2
C6H5
4-Me-C6H4
4a
4b
90
45
92
85
235-237
230-232
(234-236) [58]
(219-221) [58]
3
4-Et-C6H4
4c
4d
4e
4f
90
60
50
75
30
30
45
30
90
120
30
86
86
89
87
91
93
89
91
93
80
83
231-233
198–200
218-221
218-220
184-186
209-212
228-230
232-234
>260
(230-232) [59]
204-205 [60]
223-225 [60]
210-212 [60]
178-180 [60]
208-209 [60]
228–229 [60]
-
4
4-OH-C6H4
4-Me2N-C6H4
4-Cl-C6H4
5
6
7
4-NO2-C6H4
3-NO2-C6H4
2-NO2-C6H4
4-Ac-C6H4
4g
4h
4i
8
9
10
11
12
13
4j
c
4-CHO-C6H4
4k
4l
264-267 [61]
226-228 [58]
238-240 [60]
2-Thienyl
228-230
235-237
3-OH-4-OMe-C6H3
4m
14
15
16
17
18
19
20
21
C6H5
5a
5b
5c
5d
5e
5f
50
60
86
81
78
92
91
84
70
78
164-166
184-186
216-218
216-218
206-208
242-244
>260
168-170 [62]
182-184 [45]
205-207 [62]
196-198 [62]
190-192 [62]
-
4-Et-C6H4
4-OH-C6H4
4-NO2-C6H4
3-NO2-C6H4
4-Ac-C6H4
2-thienyl
3-indolyl
80
120
90
90
5g
5h
120
45
168-169 [63]
-
254-256
22
23
24
25
4-Me-C6H4
4-Me2N-C6H4
4-Cl-C6H4
6a
6b
6c
6d
90
60
60
60
80
83
75
93
209-211
201-203
223-224
249
198-200 [65]
218-220 [66]
243 [66]
4-NO2-C6H4
4-CHO-C6H4
249-250 [66]
26
27
6e
6f
20
60
87
83
214-216
235-237
-
c
4-CHO-C6H4
238-240 [64]
a Reaction conditions: Aldehyde (1 mmol), malononitrile (1 mmol), C–H activated ketones (1 mmol), catalyst [DMImd-DMP] in 5 mL solvent at
reflux.
b Isolated yield.
c Aldehyde (1 mmol), malononitrile (2 mmol), 5-methyl-2,4-dihydro-3H-pyrazol-3-one/dimedone (2 mmol) and catalyst [DMImd-DMP] in 5 mL
solvent at reflux.
Finally, after the tautomeric proton shift, 2-amino-4H-py-
95
ran is formed.
90
The reaction of terephthalaldehyde with equimolar
85
amounts of malononitrile, hydrazine and ethyl acetoace-
tate under optimized conditions selectively produced
80
mono-pyran (6e) in 87 % yield within 20 min, (Scheme 6).
75
However,thereactionofterephthalaldehydewithtwoequi-
1
2
3
4
Run
5
6
7
valents of malononitrile, hydrazine and ethyl acetoacetate
led to 83 % of bis-pyran (6f) after 60 min (Scheme 6).
The formation of mono-dihydropyrano[b]pyrazole
intermediate (6e), was isolated during the reaction of
(4a) yield within 90 min
(4h) yield within 30 min
Figure 1ꢂReusability of the catalyst [DMImd-DMP] in the synthesis of
compounds 4a and 4h.
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M. A. Redouane et al.: [DMImd-DMP]: A highly efficient and reusable catalyst
Scheme 5ꢂProbable mechanism for the formation of 4H-pyrans derivatives using [DMImd-DMP] as a catalyst.
Scheme 6ꢂSelective synthesis of mono- and bis-pyran: (a): terephthalaldehyde (1 mmol), malononitrile (2 mmol), hydrazine (2 mmol) and
ethyl acetoacetate (2 mmol), (b): terephthalaldehyde (1 mmol), malononitrile (1 mmol), hydrazine (1 mmol) and ethyl acetoacetate (1 mmol).
terephthalaldehyde with malononitrile (2 equiv.) and key intermediate 9 via Michael addition (Scheme 5).
5-methyl-2,4-dihydro-3H-pyrazol-3-one (2 equiv.), this However, a second Knoevenagel condensation lead
can be explained by the chemoselectivity of the cata- to bis-dihydropyrano[b]pyrazole intermediate (6f) as
lyst which involves the formation of monoaldehyde reported with other catalysts[64][67] (Scheme 7). With
intermediate (6e) by promoting the formation of the the above results, we can suggest that the [DMImd-DMP]
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Scheme 7ꢂSelective synthesis of bis-dihydropyrano[b]pyrazole, (a): terephthalaldehyde (1 mmol), malononitrile (2 mmol), hydrazine
(2 mmol) and ethyl acetoacetate (2 mmol).
facilitates the Michael reaction instead of Knoevenagel
Experimental
condensation.
General
Conclusion
Melting points (uncorrected) were measured using a
Kofler bench and are uncorrected. IR spectra were recor-
In conclusion, we report the catalytic application of ded from KBr disk on a Shimadzu FT-IR-8201 PC spectro-
1
13
ionic liquid 1,3-dimethyl imidazolium dimethyl phos- meter. The H and C NMR spectra were obtained with a
phate [DMImd-DMP] for the efficient one-pot, multi- Brüker 250 MHz spectrometer, Brüker 300 MHz spectro-
component synthesis of tetrahydrobenzo[b]pyrans and meter and Brüker 400 MHz spectrometer in DMSO-d6 (or
dihydropyrano[2,3-c]pyrazole derivatives in aqueous CDCl3). The progress of the reactions was monitored by
ethanol media. A library of 4H-pyrans was obtained in thin layer chromatography (TLC) analyses using (Merck
good to excellent yields using inexpensive and commer- 60 F254 silica gel).
cially available compounds. Also, the advantages of this
method are the operational simplicity, mild reaction con-
ditions, use of inexpensive starting materials, reusability
Procedure for the synthesis of 1,3-dimethyl imidazolium
of the catalyst, facile work-up and purification, and finally
dimethylphosphate [DMImd-DMP]:
a non-toxic solvent was used. Thus, this reaction is an
environmentally-friendly process.
Trimethylphosphate (16.7 mL, 20 mmol) was added drop-
wise to a 100 mL flask containing N-methyl imidazole (1.64
Acknowledgement: This research was supported by the g, 20 mmol) at room temperature. No temperature incre-
MESRES (Ministère de l’Enseignement Supérieur et de ase was observed on initial addition. However, when the
la Recherche Scientifique). We thank Pr. M. Lecouvey temperature was slowly increased to 140 °C. Addition was
(Faculté de Chimie of the Université Paris 13) for mass continued at 140 °C until all the material had been added
spectroscopy. We would also like to thank Pr. R. Boul- to the flask, and the reaction mixture was subsequently
cina (Université Batna 2, Algeria) and A. Khiri (Polytech- stirred for another hour. The product was moved to a
1
nique Montréal, Canada) for constant encouragement and rotary evaporator to yield viscous yellow oil.[68] H NMR
useful suggestions.
(250 MHz, CDCl3): 3.85 (d, 6H, J = 11.0 Hz, 2×CH3-O-P); 4.12
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(s, 6H, 2×N-CH3); 7.20 (s, 2H, 2× CH); 10.71(s, 1H, N=CH-N).
2-amino-7,7-dimethyl-5-oxo-4-(4-hydroxyphenyl)-
31
13C NMR (63 MHz, CDCl3): 36.0; 52.2; 123.1; 139.7. P NMR 5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4d): IR
(162 MHz, CDCl3): 2.26 (P=O).
(KBr): 3332, 2962, 2194, 1647, 1369 cm-1. 1H NMR (250 MHz,
DMSO-d6): 0.92 (s, 3H); 1.01 (s, 3H); 2.06 (d, 1H, J= 16.1 Hz);
2.22 (d, 1H, J= 16.1 Hz); 2.46 (s, 2H); 4.05 (s, 1H); 6.65 (d,
2H, J= 6.2 Hz); 6.88-6.95 (m, 4H); 9.25 (s, 1H, -OH).13C NMR
(62.9 MHz, DMSO-d6): 26.7; 28.3; 31.8; 35.4; 49.8; 57.1; 111.7;
119.3; 121.6; 121.7; 129.9; 134.1; 147.0; 147.7; 158.6; 163.1; 195.7.
2-amino-7,7-dimethyl-5-oxo-4-(4-dimethylamino-
phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(4e): IR (KBr): 3382; 2893; 2187; 1650; 1612; 1519; 1365; 1033
General Procedure for the synthesis of fused-pyranes:
A mixture of aldehyde 1 (1.0 mmol), malononitrile 2
(1.0 mmol), C-H activated carbonyl compound 3 (1 mmol),
and [DMIm-DMP] 10 mol % (or 5 mol %) was stirred and
heated in 4 mL of aqueous ethanol (1:1 v/v) for the appro-
priate time indicated in tables 4 (reaction was monitored
by TLC). After the completion of the reaction, the resulted
mixture was cooled to room temperature; 10 mL of cold
water were added, stirred for 5 min then filtered and
washed with cold water to remove the catalyst ([DMIm-
DMP] is soluble in water and the product precipitated
with high purity). The target benzopyrans and pyrano-
pyrazoles were obtained in isolated yields of 80-93% and
70-96% respectively. Finally, crude products were recrys-
tallized from EtOH to give the pure products for experi-
mental analysis.
1
cm-1. H NMR (300 MHz, DMSO-d6): 0.95 (s, 3H); 1.04 (s,
3H); 2.08 (d, 1H, J= 16.1 Hz); 2.24 (d, 1H, J= 16.1 Hz); 2.53 (s,
2H); 2.85 (s, 6H); 4.05 (s, 1H); 6.64 (d, 2H, J= 8.7 Hz); 6.86
13
(s, 2H); 6.95 (d, 2H, J= 8.8 Hz). C NMR (75 MHz, DMSO-
d6): 27.2; 28.9; 32.2; 35.1; 50.6; 59.5; 112.8; 113.8; 120.4; 128.2;
133.0; 149.7; 158.8; 162.3; 196.1.
2-amino-7,7-dimethyl-5-oxo-4-(4-chlorophenyl)-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4f): IR (KBr):
3402; 3298; 2184; 1612; 1407; 1056 cm-1. 1H NMR (300 MHz,
DMSO-d6): 0.94 (s, 3H); 1.03 (s, 3H); 2.10 (d, 1H, J= 16.1 Hz);
2.25 (d, 1H, J= 16.1 Hz); 2.51 (s, 2H); 4.19 (s, 1H); 7.03 (s, 2H);
13
7.17 (d, 2H, J= 8.4 Hz); 7.34 (d, 2H, J= 8.4 Hz). C NMR (75
Spectral data of fused-pyranes derivatives
MHz, DMSO-d6): 27.3; 28.8; 32.2; 35.5; 40.4; 50.5; 58.4; 112.7;
119.9; 128.8; 129.6; 131.6; 144.2; 158.9; 163.2; 196.2.
2-amino-7,7-dimethyl-5-oxo-4-(4-nitrophenyl)-5,6,7,8-
2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (4a): IR (KBr): 3394, 2966, tetrahydro-4H-chromene-3-carbonitrile (4g): IR (KBr):
1
2198, 1670, 1369 cm-1. H NMR (400 MHz, DMSO-d6): 0.94 3402; 3174; 2163; 1523; 1674; 1631; 1461-1407 (NO2); 1354
(s, 3H); 1.02 (s, 3H); 2.09 (d, 1H , J= 16.1 Hz); 2.24 (d, 1H, (C-N); 1022 cm-1. H NMR (250 MHz, CDCl3,): 0.93 (s, 3H);
1
J= 16.1 Hz); 2.55 (s, 2H); 4.15 (s, 1H); 6.97 (s, 2H); 7.07-7.17 1.01 (s, 3H); 2.08 (d, 1H, J= 16.0 Hz); 2.17 (d, 1H, J= 16.0
(m, 3H); 7.27 (t, 1H, J= 7.5 Hz). 13C NMR (100 MHz, DMSO- Hz); 2.48 (s, 2H); 4.34 (s, 1H); 7.16 (s, 2H); 7.42 (d, J= 8.8
d6) : 26.8; 28.4; 31.8; 35.5; 49.9; 58.4; 112.7; 119.7; 127.1; 128.3; Hz, 2H); 8.14 (d, J= 8.8 Hz, 2H). 13C NMR (62.9 MHz, CDCl3):
144.7; 158.4; 162.5; 195.6.
18.5; 26.9; 28.2; 31.8; 35.6; 49.8; 56.0; 56.9; 111.7; 119.3; 123.6;
2-amino-7,7-dimethyl-5-oxo-4-(p-tolylphenyl)-5,6,7,8- 128.6; 139.1; 146.2; 152.2; 158.5; 163.1; 195.7.
tetrahydro-4H-chromene-3-carbonitrile (4b): IR (KBr):
2-amino-7,7-dimethyl-5-oxo-4-(3-nitrophenyl)-5,6,7,8-
3375; 3178; 2187; 1678; 1639; 1365; 1141; 1029 cm-1. H NMR tetrahydro-4H-chromene-3-carbonitrile (4h): IR (KBr):
1
(250 MHz, DMSO-d6): 0,96 (s, 3H); 1.05 (s, 3H); 1.96 (d, 1H, 3433; 2958; 2191; 1596; 1249 cm-1. 1H NMR (250 MHz, CDCl3):
J= 14.8 Hz); 2.04-2.12 (m, 4H); 2,51 (s, 2H); 4.14 (s, 1H); 6.95 0.93 (s, 3H); 1.01 (s, 3H); 2.10 (d, 1H, J= 16.1 Hz); 2.24 (d, 1H,
(s, 2H, -NH2); 7.04-7.10 (m, 4H). 13C NMR (62.9 MHz, CDCl3): J= 16.3 Hz); 2.53 (s, 2H); 4.39 (s, 1H); 7.16 (s, 2H); 7.53-7.64
20.7; 26.9; 28.5; 31.8; 35.2; 50.1; 58.5; 112.9; 119.8; 127.1; 128.9; (m, 2H); 8.01-8.08 (m, 2H).13C NMR (62.9 MHz, CDCl3): 26.7;
135.7; 141.9; 158.5; 162.3; 195.7.
28.3; 31.8; 35.3: 49.8; 57.1; 111.7; 119.3; 121.6; 121.7; 130.0;
2-amino-7,7-dimethyl-5-oxo-4-(4-ethylphenyl)-5,6,7,8- 134.1; 147.0; 147.7; 158.6; 163.1; 195.7.
tetrahydro-4H-chromene-3-carbonitrile (4c): IR (KBr):
2-amino-7,7-dimethyl-5-oxo-4-(2-nitrophenyl)-5,6,7,8-
3313; 2962; 2187; 1604; 1369; 1149 cm-1. H NMR (300 MHz, tetrahydro-4H-chromene-3-carbonitrile (4i): IR (KBr): 3467;
1
DMSO-d6): 0.96 (s, 3H); 1.03 (s, 3H); 1.15 (t, 3H, J= 7.6 Hz); 2954; 2194; 1674; 1523; 1361; 1149 cm-1. H NMR (DMSO-d6,
1
2.10 (d, 1H, J= 16.1 Hz); 2.25 (d, 1H, J= 16.1 Hz); 2.52 (s, 2H); 400 MHz): 0.81 (s, 3H); 0.94 (s, 3H); 1.94 (d, 1H, J= 16.1 Hz);
2.55 (q, 2H, J= 7.6 Hz, masked by methylene signal); 4.13 (s, 2.13 (d, 1H, J= 16.1 Hz); 2.44 (s, 2H); 4.87 (s, 1H); 7.11 (s, 2H);
1H); 6.93 (s, 2H); 7.04 (d, 2H, J= 8.2 Hz); 7.12 (d, 2H, J= 8.2 7.29 (dd, 1H, J= 7.8-1.0 Hz); 7.37 (t, 1H, J= 7.2 Hz); 7.56-7.63
Hz). 13C NMR (75 MHz, DMSO-d6): 15.9; 27.3; 28.2; 28.8; 32.3; (m, 1H); 7.75 (dd, 1H, J= 8.1-0.9 Hz). 13C NMR (DMSO-d6, 100
35.6; 50.5; 59.0; 113.3; 120.3; 127.5; 128.2; 142.4; 142.5; 158.9; MHz): 26.7; 28.2; 29.9; 31.8; 49.5; 56.3; 112.4; 119.3; 123.7;
162.9; 196.2.
127.8; 130.2; 133.3; 138.9; 148.9; 159.1; 162.7; 195.8.
Unauthenticated
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M. A. Redouane et al.: [DMImd-DMP]: A highly efficient and reusableꢁ
ꢁ175
2-amino-7,7-dimethyl-5-oxo-4-(4-acetylphenyl)-5,6,7,8- 2.60 (q, 2H, J= 7.6 Hz); 4.64 (s, 1H); 7.11-7.24 (m, 6H); 7.32
tetrahydro-4H-chromene-3-carbonitrile (4j): IR (KBr): 3382 (t, 1H, J= 7.4 Hz); 7.49 (t, 2H, J= 7.5 Hz); 7.78 (d, 2H, J= 7.6
(N-H); 3201 (-NH2); 2191 (C≡N); 1651(C=O); 1600 (C=N); Hz). 13C NMR (75 MHz, DMSO-d6): 12.7; 15.5; 27.8; 36.4; 58.4;
1365 (C=C); 1415 (C-N); 1037 cm-1 (C-O-C) cm-1.1H NMR (400 98.8; 120.2; 126.2; 127.7; 127.9; 129.4; 137.6; 141.0; 142.4; 145.4;
MHz, DMSO-d6): 0.96 (s, 3H); 1.05 (s, 3H); 2.10 (d, 1H, J= 159.4.
16.2 Hz); 2.26 (d, 1H, J= 16.4 Hz); 2.55 (s, 3H); 4.27 (s, 1H);
6-amino-3-methyl-1-phenyl-4-(4-hydroxyphenyl)-1,4-
7.11 (s, 2H); 7.29 (d, 2H, J= 8.4 Hz); 7.89 (d, 2H, J= 8.6 Hz) . 13C dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5c): IR (KBr):
NMR (100 MHz, DMSO-d6): 27.2; 27.3; 28.8; 32.3; 36.1; 50.4; 3413; 3205; 2179; 1654; 1589; 1396; 1026 cm-1. 1H NMR (300
58.0; 112.6; 120.0; 128.0; 129.0; 135.9; 150.4; 159.0; 163.3; MHz, DMSO-d6): 1.79 (s, 3H); 4.56 (s, 1H); 6.72 (d, 2H, J=
196.1; 197.9. HRMS (ESI) m/z calcd for C20H21N2O3 [M+H]+ 8.5 Hz); 7.04 (d, 2H, J= 8.5 Hz); 7.10 (s, 2H); 7.31 (t, 1H, J=
337.1547, found 337.1549.
7.4 Hz); 7.49 (t, 2H, J= 7.9 Hz); 7.78 (d, 2H, J= 7.7 Hz); 9.33
13
4,4’-(1,4-phenylene)bis(2-amino-7,7-dimethyl-5-oxo- (s, 1H). C NMR (75 MHz, DMSO-d6): 13.0; 36.5; 59.3; 99.5;
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile) (4k): IR 115.7; 120.4; 126.6; 129,2; 129.8; 134.4; 138.1; 144.3; 145.8;
(KBr): 3452 (NH2); 2962 (C-H); 2195 (C≡N); 1666 (C=O); 156.7; 159.7.
1
1604 (C=N); 1365 (C=C)Ar cm-1. H NMR (400 MHz, DMSO-
6-amino-3-methyl-1-phenyl-4-(4-nitrophenyl)-1,4-dihy-
d6): 0,95 (s, 3H); 0,99 (s, 3H); 1.04 (s, 6H); 2.28-2.10 (m, dropyrano[2,3-c]pyrazole-5-carbonitrile (5d): IR (KBr):
4H); 2.56-2.47 (m, 4H); 4.15 (s, 2H); 6.96 (s, 4H, 2×NH2); 7.06 3433 (N-H); 2225 (C≡N); 1600 (C=N); 1319(C-N); 1739 (C=C);
1
(s, 4H, HAr). 13C NMR (100 MHz, DMSO-d6): 27.2; 28.2; 31.8; 1500 (C=C)Ar; 1396-1450 (NO2); 1161 cm-1 (C-O-C) cm-1. H
34.9; 49.9; 58.3; 112.7; 112.8; 119.7; 126.9; 142.8; 158.5; 162.7; NMR (250 MHz, DMSO-d6): 1.81 (s, 3H); 4.93 (s, 1H); 7.31-7.39
195.8.
(m, 3H); 7.51 (t, 2H, J= 7.6 Hz); 7.59 (d, 2H, J= 8.8 Hz), 7.80
2-amino-7,7-dimethyl-5-oxo-4-(2-thienyl)-5,6,7,8-tet- (d, 2H, J= 7.6 Hz); 8.24 (d, 2H, J= 8.8 Hz). 13C NMR (63 MHz,
rahydro-4H-chromene-3-carbonitrile (4l): IR (KBr): 3379; DMSO-d6): 12.5; 36.4; 56.9; 97.6; 119.7; 120.1; 123.9; 126.3;
3201; 2194; 1666; 1600; 1365; 1141; 1033 cm-1. H NMR (250 129.2; 129,3; 137.4; 144.0; 145.1; 146.1; 151.2; 159.7.
MHz, DMSO-d6): 1.00 (s, 3H); 1.07 (s, 3H), 2.15 (d, 1H, J=
1
6-amino-3-methyl-1-phenyl-4-(3-nitrophenyl)-1,4-
16.2 Hz); 2.26 (d, 1H, J= 16.2 Hz); 2.39 (d, 1H, J= 17 Hz); 2.49 dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5e): IR (KBr):
(d, 1H, J= 17 Hz); 4.56 (s, 1H); 6.85 (d, 2H J= 2.8 Hz); 6.90 (s, 3298 (N-H); 2191 (C≡N); 1589 (C=N); 1257(C-N); 1651 (C=C);
1
2H, -NH2); 7.16 (t, 1H, J= 2.9 Hz). 13C NMR (63 MHz, DMSO- 1446 (C=C)Ar; 1118 cm-1 (C-O-C); 1346-1446 (NO2) cm-1. H
d6): 26.4; 28.4; 30.0; 31.4; 49.7; 57.9; 112.7; 119.2; 123.5; 126.2; NMR (250 MHz, DMSO-d6): 1.88 (s, 3H); 4.96 (s, 1H); 7.28-
13
148.7; 158.5; 161.8; 195.0.
7.56 (m, 5H); 7.63-7.81 (m, 4H); 8.08-8.15 (m, 2H). C NMR
2-amino-7,7-dimethyl-5-oxo-4-(3-hydroxy-4-methoxy- (63 MHz, DMSO-d6): 12.8; 36.4; 57.3; 97.9; 120.1; 120.4; 122.4;
phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile 122.6; 126.6; 129,3; 129.6; 130.6; 134.9; 137.6; 144.2; 145.5;
1
(4m): IR (KBr): 3310, 3254, 2890, 2192, 1670, 1596 cm-1. H 146.1; 148.2; 160.0.
NMR (300 MHz, DMSO-d6): 0.96 (s, 3H); 1.03 (s, 3H); 2.09
6-amino-3-methyl-1-phenyl-4-(4-acetylphenyl)-1,
(d, 1H, J= 16.1 Hz); 2.25 (d, 1H, J= 16.1 Hz); 2.50 (s, 2H); 3.71 4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile(5f):IR(KBr):
(s, 3H); 4.01 (s, 1H); 6.51 (dd, 1H, J= 8.1 Hz, J= 2.2 Hz); 6.56 3413; 3205; 2179; 1654; 1589; 1396; 1026 cm-1. 1H NMR (400
(d, 1H, J= 2.2 Hz); 6.80 (d, 1H, J= 8.1 Hz); 6.90 (s, 2H); 8.89 MHz, DMSO-d6): 1.79 (s, 3H); 2.58 (s, 3H); 4.81 (s, 1H); 7.26-
13
(s, 1H). C NMR (75 MHz, DMSO-d6): 27.2; 28.9; 32.2; 35.3; 7.37 (m, 3H); 7.42 (d, 2H, J= 8.3 Hz); 7.50 (t, 2H, J= 7.5 Hz);
50.5; 56.1; 59.2; 112.5; 113.6; 115.0; 118.3; 120.3; 137.9; 146.7; 7.79 (d, 2H, J= 8.5 Hz); 7.96 (d, 2H, J= 8.3 Hz). 13C NMR (100
146.8; 158.9; 162.5; 196.2.
MHz, DMSO-d6): 13.0; 36.4; 59.2; 99.4; 115.6; 120.4; 120.6;
6-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3- 121.0; 126.5; 129,2; 129.7; 134.4; 137.9; 144.2; 145.9; 156.7;
c]pyrazole-5-carbonitrile (5a): IR (KBr): 3337 (N-H); 2194 159.7. HRMS (ESI) m/z calcd for C22H19N4O2 [M+H]+ 371.1503,
(C≡N); 1589 (C=N); 1261(C-N); 1658 (C=C); 1446 (C=C) Ar; found 371.1503.
1
1126 cm-1 (C-O-C) cm-1. H NMR (250 MHz, DMSO-d6): 1.79
6-amino-3-methyl-1-phenyl-4-(2-thienyl)-1,4-
(s, 3H); 4.60 (s, 1H); 6.75-7.47 (m, 10H) 7.74-7.79 (m, 2H). 13C dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5g): IR (KBr):
NMR (63 MHz, DMSO-d6): 12.6; 37.0; 58.4; 98.3; 119.9; 120.4; 3403; 3168; 2878; 2305; 1609; 1319(C-N); 1161 cm-1. 1H NMR
125.8; 126.9; 127.6; 128.3; 128.5; 129.0; 137.5; 143.8; 143.3; (300 MHz, DMSO-d6): 2.32 (s, 3H); 5.13 (s, 1H); 6.76 (sL, 1H);
145.3; 159.3.
6.91 (t, 1H, J= 3.4 Hz); 7.24 (d, 1H, J= 7.4 Hz); 7.29 (d, 1H,
13
6-amino-3-methyl-1-phenyl-4-(4-ethylphenyl)-1,4- J= 5.2 Hz), 7.45 (t, 2H, J= 7.9 Hz), 7.71 (d, 2H, J= 7.7 Hz). C
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5b): IR (KBr): NMR (75 MHz, DMSO-d6): 12.0 29.9; 62.5; 100.4; 119.6; 121.1;
3440; 3337; 2881; 2353; 2199; 1593; 1411; 1167 cm-1. H NMR 124.5; 124.6; 126.1; 127,2; 129.4; 142.6; 143.8; 146.3; 148.0;
1
(300 MHz, DMSO-d6): 1.18 (t, 3H, J= 7.6 Hz); 1.29 (s, 3H); 1 5 9.7.
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ꢁ
176ꢁ
M. A. Redouane et al.: [DMImd-DMP]: A highly efficient and reusable catalyst
6-amino-4-(1H-indol-3-yl)-3-methyl-1-phenyl-1,4- Conflict of interest: Authors state no conflict of interest.
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5h): IR (KBr):
3448 (NH); 2156 (C≡N); 1651(C=N); 1600(C=C); 1492 (C-N);
3247(-NH2) cm-1. 1H NMR (250 MHz, DMSO-d6): 2.20 (s, 3H); References
7.08-7.12 (m, 1H); 7.22-7.28 (m, 2H); 7.36 (t, 2H, J= 8.3 Hz);
[1] Dömling, A.; Ugi, I. Multicomponent reactions with
7.49 (d, 1H, J= 3.3 Hz); 7.90 (d, 2H, J= 9.4 Hz); 7.99 (d, 2H, J=
isocyanides. Angew. Chem. Int. Ed. 2000, 39, 3168-3210.
8.7 Hz); 9.75 (s, 1H). 13C NMR (63 MHz, DMSO-d6): 11.9; 37.8;
[2] Ugi, I. Recent progress in the chemistry of multicomponent
49.9; 111.1; 111.6; 116.7; 117.2; 117.4; 118.4; 120.9; 122.1; 122.7;
reactions. Pure Appl. Chem. 2001, 73, 187-192.
126.9; 127.4; 135.2; 135.3; 137.2; 137.8; 149.2; 154.91; 161.8.
6-amino-3-methyl-4-(p-tolylphenyl)-2,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitrile (6a): IR (KBr): 3479;
[3] Sunderhaus, J. D.; Martin, S. F. Applications of multicomponent
reactions to the synthesis of diverse heterocyclic scaffolds.
Chem. Eur. J. 2009, 15, 1300-1308.
1
[4] Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.;
Keating, T. A. Multiple-Component Condensation Strategies
for Combinatorial Library Synthesis. Acc. Chem. Res. 1996, 29,
123-131.
[5] Toure, B. B.; Hall, D. G. Natural product synthesis using
multicomponent reaction strategies. Chem. Rev. 2009, 109,
4439-4486.
[6] G. P. Ellis, in “Chromenes, chromanones, and chromones,”
The Chemistry of Heterocyclic Compounds Chromenes, (Eds.,
A. Weissberger and E. C. Taylor), John Wiley, New York, NY, USA,
1977, 2, 11-139.
[7] Hafez, E. A.; Elnagdi, M. H.; Elagemey, A. G. A.; El-Taweel,
F. M. A. A. Nitriles in Heterocyclic Synthesis: Novel Synthesis
of Benzo[c]coumarin and of Benzo[c]pyrano[3,2-c]quinoline
Derivatives. Heterocycles, 1987, 26, 903-907.
[8] Khafagy, M. M.; El-Wahab, A. H. F. A.; Eid, F. A.; El-Agrody, A. M.
Synthesis of halogen derivatives of benzo[h]chromene and
benzo[a]anthracene with promising antimicrobial activities.
Farmaco, 2002, 57, 715-722.
[9] Smith, W. P.; Sollis, L. S.; Howes, D. P.; Cherry, C. P.; Starkey,
D. I.; Cobley, N. K.; Weston, H.; Scicinski, J.; Merritt, A.;
Whittington, A.; Wyatt, P.; Taylor, N.; Green, D.; Bethell, R.;
Madar, S.; Fenton, R. J.; Morley, P. J.; Pateman, T.; Beresford, A.
Dihydropyrancarboxamides Related to Zanamivir:ꢀ A New
Series of Inhibitors of Influenza Virus Sialidases. 1. Discovery,
Synthesis, Biological Activity, and Structure−Activity
Relationships of 4-Guanidino- and 4-Amino-4H-pyran-6-carbo-
xamides. J. Med. Chem., 1998, 41, 787-797.
[10] Martinez, A. G.; Marco, L. J. Friedländer reaction on 2-amino-3-
cyano-4H-pyrans: Synthesis of derivatives of 4H-pyran [2, 3-b]
quinoline, new tacrine analogues. Bioorg. Med. Chem. Lett.
1997, 7, 3165–3170.
[11] Hiramoto, K.; Nasuhara, A.; Michiloshi, K.; Kato, T.; Kikugawa, K.
DNA strand-breaking activity and mutagenicity of 2,3-dihydro-3,5-
dihydroxy-6-methyl-4H-pyran-4-one (DDMP), a Maillard reaction
product of glucose and glycine. Mutat. Res. 1997, 395, 47-56.
[12] Bianchi, G.; Tava, A. Synthesis of (2R)-(+)-2,3-Dihydro-2,6-
dimethyl-4H-pyran-4-one, a Homologue of Pheromones of a
Species in the Hepialidae Family. Agric. Biol. Chem. 1987, 51,
2001-2002.
3201; 2153; 1651; 1600; 1303; 1033 cm-1. H NMR (250 MHz,
DMSO-d6): 1.78 (s, 3H,); 2.27 (s, 3H); 4.54 (s, 1H); 6.84 (s,
2H); 7.04 (d, 2H, J=7.9 Hz); 7.11 (d, 2H, J=7.7 Hz); 12.08 (s,
13
1H). C NMR (63 MHz, DMSO-d6): 9.8; 20.7; 35.8; 57.3; 97.7;
120.8; 127.4; 129.0; 135.5; 135.7; 141.5; 154.8; 160.8.
6-amino-3-methyl-4-(4-dimethylaminophenyl)-2,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (6b): IR (KBr):
3382; 2908; 2187; 1600; 1357; 1168 cm-1. 1H NMR (250 MHz,
DMSO-d6): 1.79 (s, 3H); 2.87 (s, 6H); 4.32 (s, 1H); 6.18 (s,
2H); 6.59 (d, 2H, J= 8.6 Hz); 6.96 (d, 2H, J= 8,6 Hz); 11.70 (s,
1H). 13C NMR (63 MHz, DMSO-d6): 9.7; 35.4; 58.7; 97.8; 112.0;
120.8; 127.8; 131.5; 135.4; 149.0; 154.8; 160.3.
6-amino-3-methyl-4-(4-chlorophenyl)-2,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitrile (6c): IR (KBr): 3402;
1
3298; 2183; 1407; 1612; 1408; 1056; 810 cm-1. H NMR (250
MHz, DMSO-d6): 1.77 (s, 3H); 4.52 (s, 1H); 6.57 (s, 2H); 7.12
13
(d, 2H, J=8,4 Hz); 7.22 (d, 2H, J=8,4 Hz); 11.93 (s, 1H). C
NMR (63 MHz, DMSO-d6): 9.8; 35.9; 57.5; 96.9; 120.6; 128.2;
128.7; 129.0; 129.6; 131.7; 135.8; 142.7; 154.7; 160.5; 160.8.
6-amino-3-methyl-4-(4-nitrophenyl)-2,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitrile (6d): IR (KBr): 3475; 3224;
1
2194; 1600; 1350; 1168 cm-1. H NMR (250 MHz, DMSO-d6):
1.80 (s, 3H); 4.74 (s, 1H); 6.80 (s, 2H); 7.42 (d, 2H, J= 8.0
Hz); 8.14 (d, 2H, J=6.7 Hz); 12.10 (s, 1H). 13C NMR (63 MHz,
DMSO-d6): 9.7; 36.2; 56.0; 96.3 120.4; 123.6; 128.6; 135.7;
146.3; 151.8; 161.1.
6-amino-3-methyl-4-(4-formyl)-2,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (6e): IR (KBr): 3479; 3201; 2153;
1
1651; 1600; 1303; 1033 cm-1. H NMR (250 MHz, DMSO-d6):
1.76 (s, 3H); 4.58 (s, 1H); 6.39 (s, 2H); 7.24 (d, 2H, J= 8.2
Hz); 7.84 (d, 2H, J= 8.2 Hz); 11.95 (s, 1H). 13C NMR (63 MHz,
DMSO-d6): 9.9; 36.5; 57.3; 96.6; 120.6; 127.7; 128.4; 135.5;
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