Simplified approach to the uncatalyzed knoevenagel condensation and michael addition reactions in water using microwave irradiation

Article abstract of DOI:10.1080/00397910701572696

Use of microwave irradiation in the synthesis of arylidenemalononitrile and benzopyran derivatives in water without catalyst is a clean method with high yield. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701572696

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Simplified Approach to the Uncatalyzed
Knoevenagel Condensation and Michael
Addition Reactions in Water using Microwave
Irradiation
Naglaa M. Abd El‐Rahman a , Ahmed A. El‐Kateb a & Mohamed F. Mady a
a Department of Green Chemistry, National Research Centre, Dokki, Cairo,
Egypt
Published online: 19 Nov 2007.
To cite this article: Naglaa M. Abd ElRahman , Ahmed A. ElKateb & Mohamed F. Mady (2007) Simplified
Approach to the Uncatalyzed Knoevenagel Condensation and Michael Addition Reactions in Water using
Microwave Irradiation, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 37:22, 3961-3970, DOI: 10.1080/00397910701572696
To link to this article: http://dx.doi.org/10.1080/00397910701572696
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Synthetic Communicationsw, 37: 3961–3970, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701572696
Simplified Approach to the Uncatalyzed
Knoevenagel Condensation and Michael
Addition Reactions in Water using
Microwave Irradiation
Naglaa M. Abd El-Rahman, Ahmed A. El-Kateb,
and Mohamed F. Mady
Department of Green Chemistry, National Research Centre, Dokki,
Cairo, Egypt
Abstract: Use of microwave irradiation in the synthesis of arylidenemalononitrile and
benzopyran derivatives in water without catalyst is a clean method with high yield.
Keywords: arylidinemalononitrile, microwave, reaction in water, tetrahydrobenzo[b]
pyrans
The use of microwave radiation to enhance organic reactions in environmen-
tally benign solvents such as water, which is inexpensive and not dangerous,
represents very powerful green chemical technology both from economic and
synthetic points of view. This not only reduces the burden of organic solvent
disposal but also enhances the rate of the reaction.
In recent years, the synthesis of compounds having benzopyran rings has
attracted great interest, because they have diverse pharmacological activi-
ties.[1] In addition, a large number of benzopyran derivatives possess potent
relaxant activity on blood vessels, cardiac muscle, and other smooth
muscles.[2,3] On the other hand, the pyran pharmacophore is an important
Received in the U.K. November 7, 2006
Address correspondence to Naglaa M. Abd El-Rahman, Department of Green
Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt. E-mail: naglaa_ r@
yahoo.com
3961

3962
N. M. A. El-Rahman et al.
core structure of many natural products showing antibacterial, antitumor,
antiallergic, antibiotic, hypolipidemic, and immunomodulating activites.[4]
Generally, the conventional synthesis of benzopyran derivatives involves
acid- as well as base-catalyzed condensation of the aldehydes with the active
methylene compounds in refluxing organic solvent and are plagued by the limit-
ation of prolonged reaction times, poor yields, and side reactions of aldehydes.[5]
Knoevenagel condensation and Michael addition reactions are frequently
performed in solution or without solvent under base, acid or Lewis acid
catalysis.[5–9] Other methods such as dry solid supports and microwave
heating were also applied.[10]
In continuation of our interest in heterocyclic compounds,[11,12] herein we
describe a simple and highly efficient method for the synthesis of 2-amino-4-
aryl-5-oxo-5,6,7,8-tetrahydro-4H-1-benzopyran-3-carbonitrilederivativesunder
microwave irradiation using water as a solvent.
First, we have examined this method in the Knoevenagel condensation for
the preparation of different arylidene derivatives. An equimolar quantity of the
aromatic aldehyde 1 and malononitrile 2 were mixed together in water in a
tightly closed tube and subjected to microwave irradiation from 0.5 to
2 min, and pure arylidenes 3 were obtained in excellent yields (Scheme 1).
The results are shown in Table 1.
This encouraged us to apply these simple reaction conditions in the
synthesis of benzopyran-5-one derivatives. When a mixture of arylidene 3
and dimedone 4 in water was subjected to microwave irradiation for a
suitable time (2–5 min) in a tightly closed tube, the corresponding chromene
derivatives 5 were produced efficiently without any catalyst in excellent yield
via cyclization of intermediate A (Scheme 2). The results are shown in Table 2.
The structures of the newly synthesized products were characterized by
1
IR, H NMR, and mass spectroscopy. The IR spectra of compounds 5 show
the NH2 stretching vibrations in the region 3500–3200, the CN group
1
around 2200 and the carbonyl group at 1715–1672 cm21. The H NMR
spectra of compound 5 show D2O-exchangeable signal at d 4.6–6.1 ppm
due to NH2 proton absorption. The proton on C-4 gives a singlet at 4.1–4.5
ppm. The methylene groups at C-6 and C-8 appear as singlet and multiplet
at 2.44 and 2.28 respectively. The two methyl groups on C-7 appear as two
sharp singlets at 0.96 and 1.1 ppm, indicating that protons of these two
groups are not equivalent.
These results promoted us to study the one-pot, three-component reaction
under the same conditions. Thus, when equimolar amounts of benzaldehyde,
Scheme 1.

Knoevenagel Condensation and Michael Addition
3963
Table 1. Knoevenagel condensation between aldehydes 1 and malononitrile 2 in
water using microwave irradiation
Reaction Isolated yield
(%)
Entry
Ar
time (min)
Mp (8C) Mp (8C) [Ref.]
3a
3b
3c
3d
3e
3f
C6H5
2
89
90
92
93
92
90
90
90
90
93
95
95
92
82–83
92–93
83.5–84[13]
93–94[14]
2-BrC6H4
4-BrC6H4
2-ClC6H4
4-ClC6H4
4-FC6H4
1
1
159–161 159–160[14]
1
89–90
90.5–91[15]
1
161–163 162–163[16]
125–126 126.8–127.2[15]
134–135 134–135[16]
113–114 114.5–115[17]
2
3g
3h
3i
4-CH3C6H4
4-CH3OC6H4
2-OHC6H4
4-OHC6H4
1.5
0.5
1.5
1
159–160
160[18]
3j
187–188 188–189.5[17]
118–119 119–120[14]
134–135 134–135[13]
3k
3l
2-Cl-5-NO C6H3
2
1
4-OH-3-CH3OC6H3
C4H3O
0.5
2
3m
71–72
72[18]
malononitrile, and dimedone are mixed together in water in a tightly closed
tube and subjected to microwave radiation, the corresponding pure
2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (5a)
has been obtained in a 92% yield.
Similarly, several aldehydes also reacted smoothly with malononitrile
and dimedone in water under the influence of microwave, for 3–4 min
(Scheme 3). The corresponding chromene derivatives 5 were produced effi-
ciently without the use of any catalyst in good yields (90–96%). The results
are outlined in Table 3.
All new products were characterized by IR, 1H NMR, and mass spectra.
Scheme 2.

3964
N. M. A. El-Rahman et al.
Table 2. Michael addition reaction of 3 to 4 in water using microwave irradiation
under pressure
Reaction Isolated yield
(%)
Mp (8C)
[Ref.]
Entry
Ar
time (min)
Mp (8C)
5a
5b
5c
5d
5e
5f
C6H5
4-BrC6H4
2
4
4
2
5
4
3
4
5
5
5
4
4
5
4
3
95
92
95
97
90
90
95
96
90
97
95
99
90
90
92
91
231–231 233–234[19]
196–198 197–198[19]
238–240 238–240[20]
4-ClC6H4
4-FC6H4
191–193
193[20]
2,4-(Cl)2C6H3
2,6-(Cl)2C6H3
2-Cl-5-NO 2C6H3
4-CH3OC6H4
2,4-(CH3O)2C6H3
2,4,6-(CH3O)3C6H2
4-OHC6H4
178–180 Not reported
236–238 Not reported
172–174 Not reported
194–195 194–195[20]
180–182 181–183[20]
249–251 Not reported
5g
5h
5i
5j
5k
5l
205–207
207[19]
4-OH-3-CH3OC6H3
C10H7
C7H5O2
229–231 230–231[19]
248–250 Not reported
210–212 Not reported
198–200 Not reported
209–211 Not reported
5m
5n
5o
5p
C4H3O
C4H3S
Scheme 3.
Table 3. One-pot synthesis of 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-
3-carbonitrile derivatives using microwave irradiation in water
Reaction time
(min)
Isolated yield
(%)
Entry
Ar
5a
5b
5d
5l
C6H5
4-BrC6H4
4-FC6H4
4
3
3
4
4
3
92
90
95
95
96
93
4-OH-3-CH3OC6H3
C10H7
C4H3O
5m
5o

Knoevenagel Condensation and Michael Addition
3965
In conclusion, we have demonstrated a simple and an efficient synthetic
route for arylidenemalononitrile and 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahy-
dro-4H-1-chromene-3-carbonitrile derivatives in water under microwave
irradiation to give the desired products in excellent yields. Compared to the
classical synthetic method, this approach has the advantage of being inexpen-
sive, simple, and environmentally benign.
EXPERIMENTAL
Apparatus and Analysis
All melting points were measured on a Gallenkamp melting-point apparatus
and are uncorrected. The infrared spectra were recorded in potassium
bromide disks on Pye Unicam SP 3300 and Shimadzu FT IR 8101 PC
infrared spectrophotometers. The NMR spectra were recorded on a Varian
1
Mercury VX-300 NMR spectrometer. H spectra were run at 300 MHz, and
13C spectra were run at 75.46 MHz in deuterated chloroform (CDCl3) or
dimethyl sulphoxide (DMSO-d6). Chemical shifts were related to that of the
solvent. Mass spectra were recorded on a Shimadzu GCMS-QP 1000 EX
mass spectrometer at 70 eV. Elemental analyses was carried out at the Micro-
analytical Center of Cairo University, Giza, Egypt. Microwave irradiation was
carried out by a domestic microwave oven (2450 MHz, 800 W) under atmos-
pheric pressure.
General Procedure for the Knoevenagel Condensation in Water
using Microwave Irradiation
A mixture of aromatic aldehyde (1, 0.5 mmol) and malononitrile (2,
0.5 mmol) were mixed together in water (2 ml) in a tightly closed tube and
subjected to microwave irradiation for the appropriate time until completion
of the reaction (monitored by thin-layer chromatography TLC). The precipi-
tate formed was filtered and washed with water to give the pure product 3
with sharp melting-point (see Table 1).
General Procedure for Synthesis of 2-Amino-4-aryl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile Derivatives 5
Method 1 Michael Additions
An equimolar amount of arylidene (3, 0.5 mmol) and dimedone (4, 0.5 mmol)
were allowed to react as described before under microwave irradiation, after
filtration and washing with water, to give pure product 5 (see Table 2).

3966
N. M. A. El-Rahman et al.
Method 2
One-Pot Synthesis of 5 using Microwave Irradiation in Water Equimolar
amounts of aldehyde (1, 0.5 mmol), malononitrile (2, 0.5 mmol), and
dimedone (4, 0.5 mmol) were mixed together in water (2 ml) in a tightly
closed tube and subjected to microwave irradiation as previously described.
The precipitate left after filtration and washing afforded the pure product 5
(see Table 3).
Data
2-Amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4-phenyl-4H-chromene-
3-carbonitrile (5a): Mp 231–2328C. IR (KBr) vmax/cm21: 3313, 3205
(NH2), 2211 (C N), 1688 (C55O); 1H NMR (300 MHz, CDCL3):
;;
d ¼ 1.05 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.12 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.29 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.46 (s, 2H, C6-H), 4.42 (s, 1H, C4-H),
4.58 (s, 2H, NH2, D2O exchangeable), 7.25–7.38 (m, 5H, Ar-H).
2-Amino-4-(4-bromophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-c
hromene-3-carbonitrile (5b): Mp 196–1988C. IR (KBr) vmax/cm21: 3390,
1
3285 (NH2), 2198 (C N), 1690 (C55O); H NMR (300 MHz, CDCL3):
;;
d ¼ 0.96 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.14 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.27 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.42 (s, 2H, C6-H), 4.41 (s, 1H, C4-H),
6.01 (s, 2H, NH2, D2O exchangeable), 7.35–7.48 (m, 4H, Ar-H).
2-Amino-4-(4-chlorophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5c): Mp 238–2408C. IR (KBr) vmax/cm21: 3365,
1
3200 (NH2), 2199 (C N), 1672 (C55O); H NMR (300 MHz, CDCL3):
;;
d ¼ 1.09 (s, 3H, CH3), 1.14 (s, 3H, CH3), 2.11 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.23 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.53 (s, 2H, C6-H), 4.52 (s, 1H, C4-H),
6.10 (s, 2H, NH2, D2O exchangeable), 7.15–7.38 (m, 4H, Ar-H).
2-Amino-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5d): Mp 191–1938C. IR (KBr) vmax/cm21: 3360,
1
3200 (NH2), 2201 (C N), 1678 (C55O); H NMR (300 MHz, CDCL3):
;;
d ¼ 1.00 (s, 3H, CH3), 1.09 (s, 3H, CH3), 2.19 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.28 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.57 (s, 2H, C6-H), 4.22 (s, 1H, C4-H),
5.55 (s, 2H, NH2, D2O exchangeable), 7.17–7.28 (m, 4H, Ar-H).
2-Amino-4-(2,4-dichlorophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-
4H-chromene-3-carbonitrile (5e): Mp 178–1808C. IR (KBr) vmax/cm21
:
1
;;
3388, 3267 (NH2), 2140 (C N), 1710 (C55O); H NMR (300 MHz, CDCL3):
d ¼ 1.10 (s, 3H, CH3), 1.15 (s, 3H, CH3), 2.15 (d, 1H, JAB ¼ 16 Hz, H-8a), 2.25
(d, 1H, JAB ¼ 16 Hz, H-8b), 2.57 (s, 2H, C6-H), 4.21 (s, 1H, C4-H), 5.95 (s, 2H,

Knoevenagel Condensation and Michael Addition
3967
NH2, D2O exchangeable), 7.15–7.29 (m, 3H, Ar-H). MS (m/z): 362 (Mþ).
Calcd. for C18H16Cl2N2O2 (362.24): C, 59.52; H, 4.44; N, 7.71%. Found: C,
59.65; H, 4.00; N, 7.62%.
2-Amino-4-(2,6-dichlorophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4
H-chromene-3-carbonitrile (5f): Mp 236–2388C. IR (KBr) vmax/cm21
:
3388, 3267 (NH2), 2149 (C N), 1700 (C55O); 1H NMR (300 MHz,
CDCL3): d ¼ 1.10 (s, 3H, CH3), 1.15 (s, 3H, CH3), 2.22 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.29 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.44 (s, 2H, C6-H),
4.16 (s, 1H, C4-H), 5.89 (s, 2H, NH2, D2O exchangeable), 7.17–7.31
(m, 3H, Ar-H). MS (m/z): 362 (Mþ). Calcd. for C18H16Cl2N2O2 (362.24):
C, 59.52; H, 4.44; N, 7.71%. Found: C, 59.40; H, 4.50; N, 7.77%.
;;
2-Amino-4-(2-chloro-5-nitrophenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-
oxo-4H-chromene-3-carbonitrile (5g): Mp 172–1748C. IR (KBr) vmax
/
cm21: 3370, 3250 (NH2), 2120 (C N), 1688 (C55O); H NMR (300 MHz,
CDCL3): d ¼ 1.09 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.17–2.29 (m, 2H, C8-
H), 2.48–2.55 (m, 2H, C6-H), 4.01 (s, 1H, C4-H), 5.55 (s, 2H, NH2, D2O
exchangeable), 7.23–7.39 (m, 3H, Ar-H). MS (m/z): 373 (Mþ). Calcd. for
C18H16ClN3O4 (373.79): C, 57.84; H, 4.31; N, 11.24%. Found: C, 57.96; H,
4.40; N, 11.03%.
1
;;
2-Amino-4-(4-methoxyphenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5h): Mp 194–1968C. IR (KBr) vmax/cm21: 3377,
3189 (NH2), 2156 (C N), 1676 (C55O); 1H NMR (300 MHz, CDCL3):
;;
d ¼ 1.03 (s, 3H, CH3), 1.19 (s, 3H, CH3), 2.23 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.31 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.45 (s, 2H, C6-H), 3.79 (s, 3H, OCH3),
4.02 (s, 1H, C4-H), 4.95 (s, 2H, NH2, D2O exchangeable), 7.11–7.29 (m, 4H,
Ar-H).
2-Amino-4-(2,4-dimethoxyphenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-
4H-chromene-3-carbonitrile (5i): Mp 180–1828C. IR (KBr) vmax/cm21
:
3372, 3160 (NH2), 2230 (C N), 1653 (C55O); 1H NMR (300 MHz,
CDCL3): d ¼ 0.95 (s, 3H, CH3), 1.03 (s, 3H, CH3), 2.11 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.29 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.53 (s, 2H, C6-H),
3.71 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 4.23 (s, 1H, C4-H), 5.45 (s, 2H,
NH2, D2O exchangeable), 7.01–7.37 (m, 3H, Ar-H).
;;
2-Amino-4-(2,4,6-trimethoxyphenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-
oxo-4H-chromene-3-carbonitrile (5j): Mp 249–2518C. IR (KBr) vmax
/
cm21: 3382, 3150 (NH2), 2235 (C N), 1670 (C55O); H NMR (300 MHz,
CDCL3): d ¼ 1.01 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.11 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.23 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.44 (s, 2H, C6-H),
3.75 (s, 3H, OCH3), 3.81 (s, 6H, 2OCH3), 4.33 (s, 1H, C4-H), 5.32 (s, 2H,
NH2, D2O exchangeable), 7.21–7.35 (m, 2H, Ar-H).
1
;;

3968
N. M. A. El-Rahman et al.
2-Amino-4-(4-hydroxyphenyl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5 k): Mp 205–2078C. IR (KBr) vmax/cm21: 3650
1
(OH), 3325,3100 (NH2), 2195 (C N), 1679 (C55O); H NMR (300 MHz,
;;
CDCL3): d ¼ 1.05 (s, 3H, CH3), 1.14 (s, 3H, CH3), 2.12 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.23 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.44 (s, 2H, C6-H),
4.33 (s, 1H, C4-H), 5.59 (s, 2H, NH2, D2O exchangeable), 7.01–7.33 (m, 4H,
Ar-H), 8.1 (br s, 1H, OH, D2O exchangeable).
2-Amino-4-(3-hydroxy-4-methoxphenyl)-5,6,7,8-tetrahydro-7,7-dimethyl
-5-oxo-4H-chromene-3-carbonitrile (5l): Mp 229–2318C. IR (KBr) vmax
/
cm21: 3440 (OH), 3310, 3172 (NH2), 2240 (C N), 1680 (C55O); 1H
NMR (300 MHz, CDCL3): d ¼ 1.05 (s, 3H, CH3), 1.20 (s, 3H, CH3), 2.22
(d, 1H, JAB ¼ 16 Hz, H-8a), 2.32 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.50 (s, 2H,
C6-H), 3.75 (s, 3H, OCH3), 4.52 (s, 1H, C4-H), 5.15 (s, 2H, NH2, D2O
exchangeable), 7.21–7.42 (m, 4H, Ar-H), 7.61 (br s, 1H, OH, D2O
exchangeable).
;;
2-Amino-4-(naphthalen-2-yl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5 m): Mp 248–2508C. IR (KBr) vmax/cm21
:
3379, 3170 (NH2), 2236 (C N), 1678 (C55O); 1H NMR (300 MHz,
DMSO- d6): d ¼ 0.96 (s, 3H, CH3), 1.05 (s, 3H, CH3), 2.15 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.29 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.55 (s, 2H, C6-H),
4.34 (s, 1H, C4-H), 5.51 (s, 2H, NH2, D2O exchangeable), 6.99–7.39
(m, 7H, Ar-H). MS (m/z): 344 (Mþ). Calcd. for C22H20N2O2 (344.41): C,
76.72; H, 5.85; N, 8.13%. Found: C, 76.90; H, 5.80; N, 8.00%.
;;
2-Amino-4-(benzo[d][1,3]dioxol-5-yl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-
oxo-4H-chromene-3-carbonitrile (5n): Mp 210–2128C. IR (KBr) vmax
/
cm21: 3388, 3179 (NH2), 2240 (C N), 1675 (C55O); H NMR (300 MHz,
DMSO-d6): d ¼ 1.06 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.12 (d, 1H,
JAB ¼ 16 Hz, H-8a), 2.27 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.49 (s, 2H, C6-H),
4.33 (s, 1H, C4-H), 4.59 (s, 2H, NH2, D2O exchangeable), 5.91 (s, 2H,
CH2) 6.69–6.74 (m, 3H, Ar-H); 13C NMR (DMSO-d6), d ¼ 195.65 (CO),
162.32 (C-8a), 158.47 (C-2), 147.23, 145.89, 138.89, 120.34 (4C), 119.70
(CN), 112.84 (C-4a), 108.01, 107.58 (2C), 100.91 (1C)., 58.61 (C-3), 50.11
(C-6), 39.9 (C-8), 35.30 (C-4), 31.8 (C-7), 28.35, 27.00. MS (m/z): 338
(Mþ). Calcd. for C19H18N2O4 (338.36): C, 67.44; H, 5.36; N, 8.28%.
Found: C, 67.30; H, 5.40; N, 8.38%.
1
;;
2-Amino-4-(fur-2-yl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromen
e-3-carbonitrile (5o): Mp 198–2008C. IR (KBr) vmax/cm21: 3374, 3146
(NH2), 2235 (C N), 1679 (C55O); 1H NMR (300 MHz, CDCL3):
;;
d ¼ 1.06 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.17 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.29 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.46 (s, 2H, C6-H), 4.58 (s, 1H, C4-H),
4.79 (s, 2H, NH2, D2O exchangeable), 6.18–7.27 (m, 3H, furyl-H); 13C

Knoevenagel Condensation and Michael Addition
3969
NMR (DMSO-d6), d ¼ 195.22 (CO), 159.12 (C-8a), 158.98 (C-2), 150.01,
140.87, (2C), 119.80 (CN), 112.89 (C-4a), 111.00, 108.25 (2C), 60.10
(C-3), 49.23 (C-6), 39.88 (C-8), 37.24 (C-4), 32.69 (C-7), 28.18, 27.45. MS
(m/z): 284 (Mþ). Calcd. for C16H16N2O3 (284.31): C, 67.59; H, 5.67; N,
9.85%. Found: C, 67.39; H, 5.72; N, 10.00%.
2-Amino-4-(thien-2-yl)-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chrom
ene-3-carbonitrile (5p): Mp 209–2118C. IR (KBr) vmax/cm21: 3369, 3146
(NH2), 2235 (C N), 1685 (C55O); 1H NMR (300 MHz, DMSO- d6):
;;
d ¼ 1.06 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.15 (d, 1H, JAB ¼ 16 Hz, H-8a),
2.24 (d, 1H, JAB ¼ 16 Hz, H-8b), 2.48 (s, 2H, C6-H), 4.51 (s, 1H, C4-H),
4.80 (s, 2H, NH2, D2O exchangeable), 6.67–7.02 (m, 3H, thienyl-H); 13C
NMR (DMSO-d6), d ¼ 193.15 (CO), 160.02 (C-8a), 159.05 (C-2), 140.81,
127.25, 126.99, 122.00 (4C), 119.71 (CN), 111.23 (C-4a), 59.00 (C-3),
50.56 (C-6), 39.42 (C-8), 36.31 (C-4), 31.8 (C-7), 28.15, 27.06. MS (m/z):
300 (Mþ). Calcd. for C16H16N2O2S (300.38): C, 63.98; H, 5.37; N, 9.33; S,
10.68%. Found: C, 64.19; H, 5.30; N, 9.30; S, 10.56%.
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