Diammonium hydrogen phosphate: An efficient and versatile catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous media

Article abstract of DOI:10.1080/00397910701196579

Diammonium hydrogen phosphate was used as a mild, efficient, neutral, and cheap catalyst for the synthesis of various 4H-benzo[b]pyran derivatives via a one-pot, three-component condensation of aromatic aldehydes, active methylene compounds, and dimedone in aqueous media. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701196579

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Diammonium Hydrogen Phosphate:
An Efficient and Versatile Catalyst
for the One‐Pot Synthesis of
Tetrahydrobenzo[b]pyran Derivatives in
Aqueous Media
Saeed Balalaie a , Morteza Bararjanian a , Masoumeh Sheikh‐Ahmadi a
,
Shohreh Hekmat b & Peyman Salehi c
a Department of Chemistry , K. N. Toosi University of Technology , Tehran,
Iran
b Department of Chemistry , Islamic Azad University , North Tehran Branch,
Iran
c Department of Phtochemistry , Medicinal Plants and Drugs Research
Institute, Shahid Beheshti University , Evin, Tehran, Iran
Published online: 13 Oct 2010.
To cite this article: Saeed Balalaie , Morteza Bararjanian , Masoumeh Sheikh‐Ahmadi , Shohreh Hekmat
& Peyman Salehi (2007) Diammonium Hydrogen Phosphate: An Efficient and Versatile Catalyst for the
One‐Pot Synthesis of Tetrahydrobenzo[b]pyran Derivatives in Aqueous Media, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:7, 1097-1108, DOI:
10.1080/00397910701196579
To link to this article: http://dx.doi.org/10.1080/00397910701196579
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Synthetic Communicationsw, 37: 1097–1108, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701196579
Diammonium Hydrogen Phosphate: An
Efficient and Versatile Catalyst for the One-
Pot Synthesis of Tetrahydrobenzo[b]pyran
Derivatives in Aqueous Media
Saeed Balalaie, Morteza Bararjanian, and
Masoumeh Sheikh-Ahmadi
Department of Chemistry, K. N. Toosi University of Technology,Tehran,
Iran
Shohreh Hekmat
Department of Chemistry, Islamic Azad University, North Tehran
Branch, Iran
Peyman Salehi
Department of Phtochemistry, Medicinal Plants and Drugs Research
Institute, Shahid Beheshti University, Evin, Tehran, Iran
Abstract: Diammonium hydrogen phosphate was used as a mild, efficient, neutral, and
cheap catalyst for the synthesis of various 4H-benzo[b]pyran derivatives via a one-pot,
three-component condensation of aromatic aldehydes, active methylene compounds,
and dimedone in aqueous media.
Keywords: aqueous media, 4H-benzo[b]pyrans, diammonium hydrogen phosphate,
Knoevenagel cyclocondensation
Received in Poland August 22, 2006
Address correspondence to Saeed Balalaie, Department of Chemistry, K. N. Toosi
University of Technology, P. O. Box 15875-4416, Tehran, Iran. E-mail: balalaie@
kntu.ac.ir
1097

1098
S. Balalaie et al.
INTRODUCTION
The development of environmentally friendly catalysts and solvents for
organic chemistry and finding neutral conditions are broad areas of consider-
able importance. From both economical and environmental points of view, the
use of nontoxic solvents and nonmetallic catalysts is very promising. In the
past few years, room-temperature reactions in water as solvent using neutral
catalysts have been recognized as possible environmentally benign alterna-
tives to volatile chemical solvents.[1]
4H-Benzo[b]pyrans and their derivatives are of considerable interest
because of their wide range of biological activities.[2] These compounds
show diverse pharmacological properties such as spasmolytic, diuretic, antic-
oagulant, anticancer, and antianaphylactic activities.[3] Also, they can be used
as cognitive enhancers for the treatment of neurodegenerative disease,
including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s
disease, Parkinson’s disease, AIDS-associated dementia, and Down
syndrome, as well as for the treatment of schizophrenia and myoclonus.[4]
4H-Pyran units could also be found in the structure of a series of natural
products.[5] A number of 2-amino-4H-pyran derivatives are useful as photoac-
tive materials.[6]
4H-Benzo[b]pyrans are conventionally synthesized using organic
solvents such as DMF or acetic acid.[7,8] However, these solvents make the
work-up procedure complicated, lead to poor yields of products, and pollute
the environment. The use of microwave[9] and ultrasound irradiations are
also reported for the synthesis of pyrans.[10] Recently, some two-[11] and
three-component[12,13] condensations have been introduced for the synthesis
of benzo[b]pyrans. In spite of the merits of these procedures, each of them
suffers at least from one of the following limitations: low yields, unavailabli-
lity of the reagents, long reaction times, effluent pollution, harsh reaction con-
ditions, and tedious work-up procedures.
Diammonium hydrogen phosphate, (NH4)2HPO4, is a very cheap,
nontoxic, and water-soluble salt, and the pH of its aqueous solution (5 g/
100 ml) is in the range of 7.8–8.1. This reagent has been used in the manufac-
turing of many important materials, such as fire-proofing textiles, paper, wood,
and vegetable fibers.[14] It has also been used as a corrosion inhibitor and
Scheme 1.

Diammonium Hydrogen Phosphate
1099
fertilizer.[15] Diammonium hydrogen phosphate is a commercially available
compound that can be used in the laboratory without any special precaution.
To the best of our knowledge, there are few reports on the application of
diammonium hydrogen phosphate in organic synthetic methodology.[16]
Table 1. Diammonium hydrogen phosphate–catalyzed synthesis of 4 H-benzo[b]
pyrans 4A (a–l) and 5B (a–s) in aqueous media
Mp (8C)
Yieldb
Product
Ar
R
Methoda (%)
Found
Reported
4a
4b
4c
4d
4e
4f
C6H5
CN
CN
A
A
A
A
A
A
A
A
A
A
A
A
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
97
91
87
84
82
83
83
95
97
90
96
78
94
89
81
84
88
82
86
90
83
81
80
78
90
86
81
90
90
89
80
231–235 226–228[8]
207–209 196–198[9]
236–237 224–225[12]
213–215 207–209[8]
227–230
4-Br-C6H4
3-Cl-C6H4
4-Cl-C6H4
CN
CN
4-CN-C6H4
2,3-Cl2-C6H3
2,4-Cl2-C6H3
3-OH-C6H4
4-OH-C6H4
4-CH3-C6H4
3-NO2-C6H4
4-NO2-C6H4
C6H5
CN
CN
249–250 255–257[17h]
192–195 192–194[17h]
230–235 236–238[17h]
204–205 206–208[9]
219–222 214–216[12b]
213–217 208–211[12b]
181–184 177–178[12b]
149–150 146–148[8]
158–160 158–160[8]
165–169
4g
4h
4i
CN
CN
CN
CN
4j
4k
4l
CN
CN
5a
5b
5c
5d
5e
5f
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH2CH3
CO2CH3
CO2CH2CH3
C6H5
4-Br-C6H4
4-Br-C6H4
2-Cl-C6H4
159–163 160–162[12c]
198–200 198–200[8]
4-Cl-C6H4
4-Cl-C6H4
171
150
167–168[8]
150–152[8]
5g
5h
5i
4-CN-C6H4
2,3-Cl2-C6H3
2,3-Cl2-C6H3
2,4-Cl2-C6H3
2,4-Cl2-C6H3
4-OCH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
3-NO2-C6H4
3-NO2-C6H4
4-NO2-C6H4
4-NO2-C6H4
177–179
164–169
174–176
214–218
172–174 170–172[10]
130–133
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
176–178 172–174[8]
154–155 156–157[8]
190–191 190–192[10]
169–172 172–174[12c]
186–188
179–181 181–183[10]
aA: The reaction was conducted in H2O at room temperature; B: The reaction was
carried out in H2O/EtOH (1:1) at 508C.
1
bYields refer to those of pure isolated products characterized by IR and H NMR
spectroscopic data.

1100
S. Balalaie et al.
As part of our ongoing work on one-pot multicomponent reactions
(MCRs) for the synthesis of various biologically active heterocyclic
compounds,[17] we now report a highly efficient procedure for the preparation
of 4H-benzo[b]pyrans via a one-pot, three-component tandem Knoevenagel
cyclocondensation reaction using diammonium hydrogen phosphate as
catalyst in aqueous media (Scheme 1).
RESULTS AND DISCUSSION
When malononitrile, aromatic aldehyde, and dimedone were treated with
diammonium hydrogen phosphate (10 mol%) in water at room temperature
Scheme 2. Proposed mechanism for diammonium hydrogen phosphate (10%)–
catalyzed synthesis of 4H-benzo[b]pyrans 4A and 5B in aqueous media.

Diammonium Hydrogen Phosphate
1101
(method A), the desired 2-amino-3-cyano-4-aryl-7,7-dimethyl-5-oxo-4H-
5,6,7,8-tetrahydrobenzo[b]pyran derivatives 4A (a–l) were obtained in
high to excellent yields (78–97%) within a very short period of time
(0.5-2 h). Because of the low solubility of the alkylcyanoacetates in
water, their three-component condensation with dimedone and benzal-
dehyde was carried out in aqueous ethanol (1:1, H2O:EtOH) at 508C.
The reactions were performed in the presence of 10 mol% of diammonium
hydrogen phosphate at 508C, which led to 2-amino-3-alkylcarboxy-4-aryl-
7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran derivatives 5B
(a–s). The results are summarized in Table 1. Longer reaction times and
higher temperatures (508C) were used for condensation of alkylcyanoace-
tates. This could be attributed to the lower reactivities of the cyanoacetates
compared to malononitrile.
A proposed mechanism for the synthesis of benzopyrans is outlined in
Scheme 2. Based on this mechanism, diammonium hydrogen phosphate is
an effective catalyst for the formation of olefin 7, readily prepared in situ
from Knoevenagel condensation of aryl aldehyde 1 and active methylene
compound 2. Diammonium hydrogen phosphate (DAHP) can form iminium
5, which is reactive in reaction with active methylene compound 2 to form
intermediate 6, which could be converted to olefin 7 after dehydration.
Meanwhile, dimedone can form enamine 8, which could easily react with
olefin 7, resulting in formation of intermediate 9, which is converted
to product 4 after proton transfer, tautomerization and hyrolysis in water
media.
The three-component reaction of 3-nitro benzaldehyde, dimedone,
methylcyanoacetate at 508C in a mixture of water and ethanol (1:1) as
solvent for 10 h in the absence of diammonium hydrogen phosphate yields
alkene 7, and no benzo[b]pyran (5r) was formed. Prolonging the reaction to
28 h in the same condition results in the formation of a trace amount of ben-
zo[b]pyran (5r). This proves the essential effect of diammonium hydrogen
phosphate as a catalyst in the progress the reaction.
In conclusion, we have demonstrated a rapid and very efficient diammonium
hydrogen phosphate–catalyzed one-pot, three-component synthesis of tetrahy-
drobenzo[b]pyran derivatives in aqueous media. The current methodology has
the advantages of operational simplicity, neutral and mild reaction conditions,
high to excellent yields of products, lack of toxicity, and low costs.
EXPERIMENTAL
Melting points were determined with Electrothermal 9100 apparatus and are
uncorrected. IR spectra were obtained on Shimadzu IR-460 and ABB FT-IR
1
(FTLA 2000) spectrometers. H NMR spectra were run on a Bruker DRX-
300 (300-MHz) and DRX-500 (500-MHz) Avance instrument using TMS as
internal standard and DMSO-d6 or CDCl3 as solvent.

1102
S. Balalaie et al.
General Experimental Procedure: Method A
A mixture of an aromatic aldehyde (1, 1 mmol), malononitrile (2, 1.2 mmol),
dimedone (3, 1.1 mmol), and diammonium hydrogen phosphate (0.013 g,
10 mol%) in H2O (20 mL) was stirred at room temperature for 0.5–2 h.
After completion of the reaction as confirmed by thin-layer chromatography
(TLC), the mixture was filtered. The remaining solid compound was
washed with H2O (20 mL) and finally was purified by recrystallization from
EtOH (96%).
General Experimental Procedure: Method B
A mixture of aromatic aldehyde (1, 1 mmol), alkyl cyanoacetate (2,
1.2 mmol), dimedone (3, 1.1 mmol), and diammonium hydrogen phosphate
(0.013 g, 10 mol%) in H2O–EtOH (1:1, 15 mL) was stirred at 508C for
1.5–5 h. After completion of the reaction, the volume of the solution was
reduced to half, and water (15 ml) was added. Then the mixture was cooled
in a fridge overnight. The precipitated solid compound was collected by fil-
tration and recrystallized from EtOH (96%).
Selected Data for Compounds 4A (a–l) and 5B (a–s)
1
4a: IR (KBr): nmax ¼ 3394, 3324, 3029, 2962, 2197, 1678 cm21. H NMR
(DMSO-d6): d ¼ 0.95 (3H, s, Me), 1.04 (3H, s, Me), 2.10 (1H, d,
J ¼ 16.0 Hz, H-6), 2.25 (1H, d, J ¼16.0 Hz, H-60), 2.49 (2H, brs, CH2),
4.16 (1H, s, H-4), 7.02 (2H, brs, NH2), 7.17 (3H, m, H-Ar), 7.29 (2H, m,
H-Ar).
4b: IR (KBr): nmax ¼ 3389, 3322, 2958, 2188, 1676 cm21
.
1H NMR
(DMSO-d6): d ¼ 0.94 (3H, s, Me), 1.04 (3H, s, Me), 2.09 (1H, d,
J ¼ 16.0 Hz, H-6), 2.26 (1H, d, J ¼16.0 Hz, H-60), 2.50 (2H, brs, CH2),
4.17 (1H, s, H-4), 7.08 (2H, brs, NH2), 7.10 (2H, d, J ¼ 8.3 Hz, H-Ar),
7.48 (2H, d, J ¼ 8.3 Hz, H-Ar).
1
4e: IR (KBr):nmax ¼ 3378, 3352, 2962, 2229, 2190, 1686 cm21. H NMR
(DMSO-d6): d ¼ 0.95 (3H, s, Me), 1.03 (3H, s, Me), 2.10 (1H, d,
J ¼ 16.0 Hz, H-6), 2.25 (1H, d, J ¼ 16.0 Hz, H-60), 2.50 (2H, brs, CH2),
4.29 (1H, s, H-4), 7.20 (2H, brs, NH2), 7.34 (2H, d, J ¼ 7.65 Hz, H-Ar),
7.76 (2H, d, J ¼ 7.20 Hz, H-Ar).
1
4f: IR (KBr): nmax ¼ 3445, 3322, 3198, 2962, 2192, 1680 cm21. H NMR
(DMSO-d6): d ¼ 0.98 (3H, s, Me), 1.04 (3H, s, Me), 2.08 (1H, d,
J ¼ 16.0 Hz, H-6), 2.24 (1H, d, J ¼16.0 Hz, H-60), 2.50 (2H, brs, CH2),

Diammonium Hydrogen Phosphate
1103
4.78 (1H, s, H-4), 7.12 (2H, brs, NH2), 7.16 (1H, d, J ¼ 7.8 Hz, H-Ar), 7.30
(1H, t, J ¼ 7.8 Hz, H-Ar), 7.48 (1H, d, J ¼ 7.8 Hz, H-Ar).
4h: IR (KBr): nmax ¼ 3455, 3311, 2964, 2192, 1678 cm21
.
1H NMR
(DMSO-d6): d ¼ 0.96 (3H, s, Me), 1.04 (3H, s, Me), 2.10 (1H, d,
J ¼ 16.0 Hz, H-6), 2.25 (1H, d, J ¼ 16.0 Hz, H-60), 2.50 (2H, brs, CH2),
4.06 (1H, s, H-4), 6.56 (3H, m, H-Ar), 6.99 (2H, brs, NH2), 7.06 (1H, t,
J ¼ 7.9 Hz, H-Ar).
4i: IR (KBr): nmax ¼ 3327, 3188, 2957, 2192, 1683 cm21. 1H NMR (DMSO-
d6): d ¼ 0.94 (3H, s, Me), 1.03 (3H, s, Me), 2.08 (1H, d, J ¼ 16.0 Hz, H-6),
2.24 (1H, d, J ¼ 16.0 Hz, H-60), 2.49 (2H, brs, CH2), 4.06 (1H, s, H-4),
6.65 (2H, d, J ¼ 8.2 Hz, H-Ar), 6.92 (2H, d, J ¼ 8.2 Hz, H-Ar), 6.93 (2H,
brs, NH2).
4j: IR (KBr): nmax ¼ 3424, 3326, 2958, 2190, 1678 cm21. 1H NMR (DMSO-
d6): d ¼ 0.94 (3H, s, Me), 1.03 (3H, s, Me), 2.07 (1H, d, J ¼ 16.0 Hz, H-6),
2.23 (1H, d, J ¼ 16.0 Hz, H-60), 2.24 (3H, s, Me), 2.50 (2H, brs, CH2), 4.11
(1H, s, H-4), 6.97 (2H, brs, NH2), 7.01 (2H, d, J ¼ 8.0 Hz, H-Ar), 7.08 (2H,
d, J ¼ 8.0 Hz, H-Ar)
4k: IR (KBr): nmax ¼ 3429, 3332, 3198, 2925, 2187, 1687, 1531, 1350 cm21
.
1H NMR (DMSO-d6): d ¼ 0.95 (3H, s, Me), 1.04 (3H, s, Me), 2.11 (1H, d,
J ¼ 16.0 Hz, H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.50 (2H, brs, CH2),
4.41 (1H, s, H-4), 7.20 (2H, brs, NH2), 7.64 (2H, m, H-Ar), 7.97 (1H, brs,
H-Ar), 8.07 (1H, d, J ¼ 7.7 Hz, H-Ar).
1
4l: IR (KBr): nmax ¼ 3408, 3322, 2962, 2162, 1670, 1523, 1349 cm21. H
NMR (DMSO-d6): d ¼ 0.95 (3H, s, Me), 1.04 (3H, s, Me), 2.10 (1H, d,
J ¼ 16.0 Hz, H-6), 2.25 (1H, d, J ¼ 16.0 Hz, H-60), 2.50 (2H, brs, CH2),
4.36 (1H, s, H-4), 7.20 (2H, brs, NH2), 7.45 (2H, d, J ¼ 7.0 Hz, H-Ar), 8.18
(2H, d, J ¼ 7.0 Hz, H-Ar).
1
5a: IR (KBr): nmax ¼ 3421, 3304, 2960, 1695, 1656, 1622 cm21. H NMR
(CDCl3): d ¼ 1.0 (3H, s, Me), 1.13 (3H, s, Me), 2.20 (1H, d, J ¼ 16.0 Hz,
H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, brs, CH2), 3.64 (3H, s,
OMe), 4.75 (1H, s, H-4), 6.20 (2H, brs, NH2), 7.14 (1H, m, H-Ar), 7.24
(2H, m, H-Ar), 7.29 (2H, brs, H-Ar).
1
5b: IR (KBr): nmax ¼ 3404, 3291, 1691, 1655 cm21. H NMR (CDCl3):
d ¼ 1.0 (3H, s, Me), 1.13 (3H, s, Me), 1.19 (3H, t, J ¼ 7.1 Hz, Me), 2.20
(1H, d, J ¼ 16.0 Hz, H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, brs,
CH2), 4.06 (2H, m, OCH2), 4.73 (1H, s, H-4), 6.22 (2H, brs, NH2), 7.14
(1H, t, J ¼ 7.20 Hz, H-Ar), 7.24 (2H, t, J ¼ 7.20 Hz, H-Ar), 7.30 (2H, d,
J ¼ 7.50 Hz, H-Ar).

1104
S. Balalaie et al.
5c: IR (KBr): nmax ¼ 3472, 3317, 2960, 2347, 1692, 1669, 1620, 1522 cm21
.
1H NMR (CDCl3): d ¼ 1.0 (3H, s, Me), 1.13 (3H, s, Me), 2.20 (1H, d,
J ¼ 16.0 Hz, H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.45 (2H, brs, CH2),
3.63 (3H, s, OMe), 4.70 (1H, s, H-4), 6.25 (2H, brs, NH2), 7.18 (2H, d,
J ¼ 8.4 Hz, H-Ar), 7.36 (2H, d, J ¼ 8.4 Hz, H-Ar).
1
5d: IR (KBr): nmax ¼ 3475, 3333, 1687, 1656 cm21. H NMR (CDCl3):
d ¼ 1.01 (3H, s, Me), 1.14 (3H, s, Me), 1.19 (3H, t, J ¼ 7.1 Hz, Me), 2.20
(1H, d, J ¼ 16.0 Hz, H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.45 (2H, brs,
CH2), 3.63 (3H, s, OMe), 4.70 (1H, s, H-4), 6.25 (2H, brs, NH2), 7.18 (2H,
d, J ¼ 8.4 Hz, H-Ar), 7.36 (2H, d, J ¼ 8.4 Hz, H-Ar).
5e: IR (KBr): nmax ¼ 3423, 3314, 1694, 1652, 1612 cm21. 1H NMR (CDCl3):
d ¼ 1.04 (3H, s, Me), 1.16 (3H, s, Me), 2.18 (1H, d, J ¼ 16.0 Hz, H-6), 2.26
(1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, brs, CH2), 3.63 (3H, s, OMe), 5.06 (1H,
s, H-4), 6.26 (2H, brs, NH2), 7.08 (1H, dt, J ¼ 7.8, 1.6 Hz, H-Ar), 7.17 (1H, t,
J ¼ 7.50 Hz, H-Ar), 7.27 (1H, d, J ¼ 7.5 Hz, H-Ar), 7.30 (1H, d, J ¼ 7.50 Hz,
H-Ar).
5f: IR (KBr): nmax ¼ 3429, 3313, 1694, 1653, 1615 cm21. 1H NMR (CDCl3):
d ¼ 1.0 (3H, s, Me), 1.14 (3H, s, Me), 2.20 (1H, d, J ¼ 16.0 Hz, H-6), 2.27
(1H, d, J ¼ 16.0 Hz, H-60), 2.45 (2H, brs, CH2), 3.65 (3H, s, OMe), 4.73
(1H, s, H-4), 6.20 (2H, brs, NH2), 7.21 (2H, d, J ¼ 8.4 Hz, H-Ar), 7.24 (2H,
d, J ¼ 8.4 Hz, H-Ar).
5g: IR (KBr): nmax ¼ 3477, 3317, 1692, 1669 cm21
.
1H NMR (CDCl3):
d ¼ 0.98 (3H, s, Me), 1.11 (3H, s, Me), 1.17 (3H, t, J ¼ 7.1 Hz, Me), 2.17
(1H, d, J ¼ 16.0 Hz, H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.44 (2H, brs,
CH2), 4.05 (2H, s, OMe), 4.68 (1H, s, H-4), 6.20 (2H, brs, NH2), 7.19 (2H,
d, J ¼ 8.1 Hz, H-Ar), 7.21 (2H, d, J ¼ 8.1 Hz, H-Ar).
5h: IR (KBr): nmax ¼ 3440, 3324, 2227, 1687, 1658 cm21. 1H NMR (CDCl3):
d ¼ 0.99 (3H, s, Me), 1.14 (3H, s, Me), 2.18 (1H, d, J ¼ 16.0 Hz, H-6), 2.28
(1H, d, J ¼ 16.0 Hz, H-60), 2.47 (2H, brs, CH2), 3.62 (3H, s, OMe), 4.78 (1H,
s, H-4), 6.28 (2H, brs, NH2), 7.41 (2H, d, J ¼ 7.1 Hz, H-Ar), 7.54 (2H, d,
J ¼ 7.1 Hz, H-Ar).
1
5i: IR (KBr): nmax ¼ 3408, 3302, 2957, 1696, 1655, 1619 cm21. H NMR
(CDCl3): d ¼ 1.03 (3H, s, Me), 1.15 (3H, s, Me), 2.19 (1H, d, J ¼ 16.0 Hz,
H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, brs, CH2), 3.60 (3H, s, OMe),
5.10 (1H, s, H-4), 6.30 (2H, brs, NH2), 7.10 (1H, t, J ¼ 7.80 Hz, H-Ar), 7.24
(1H, dd, J ¼ 7.8,1.5 Hz, H-Ar), 7.28 (1H, dd, J ¼ 7.8,1.5 Hz, H-Ar).
1
5j: IR (KBr): nmax ¼ 3418, 3303, 2962, 1694, 1652 cm21. H NMR (CDCl3):
d ¼ 1.04 (3H, s, Me), 1.14 (3H, s, Me), 1.16 (3H, t, J ¼ 7.1 Hz, Me), 2.19 (1H,

Diammonium Hydrogen Phosphate
1105
d, J ¼ 16.0 Hz, H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, brs, CH2), 4.05
(2H, m, OCH2), 5.10 (1H, s, H-4), 6.30 (2H, brs, NH2), 7.1 (1H, t, J ¼ 7.8 Hz,
H-Ar), 7.27 (1H, d, J ¼ 7.8 Hz, H-Ar), 7.3 (1H, d, J ¼ 7.8 Hz, H-Ar).
1
5k: IR (KBr): nmax ¼ 3421, 3310, 2957, 1696, 1652, 1614 cm21. H NMR
(CDCl3): d ¼ 1.04 (3H, s, Me), 1.14 (3H, s, Me), 2.18 (1H, d, J ¼ 16.0 Hz,
H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.43 (1H, d, J ¼ 17.6, H-8), 2.48
(1H, d, J ¼ 17.6, H-80), 3.61 (3H, s, OMe), 5.0 (1H, s, H-4), 6.28 (2H, brs,
NH2), 7.15 (1H, dd, J ¼ 8.3, 2.2 Hz, H-Ar), 7.25 (1H, d, J ¼ 8.3 Hz, H-Ar),
7.30 (1H, d, J ¼ 2.2 Hz, H-Ar).
5l: IR (KBr): nmax ¼ 3446, 2964, 1694, 1656, 1619 cm21. 1H NMR (CDCl3):
d ¼ 1.04 (3H, s, Me), 1.14 (3H, s, Me), 1.18 (3H, t, J ¼ 7.1 Hz, Me), 2.18 (1H,
d, J ¼ 16.0 Hz, H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.46 (2H, m, CH2), 4.06
(2H, m, OCH2), 5.0 (1H, s, H-4), 6.30 (2H, brs, NH2) 7.15 (1H, dd, J ¼ 4.6,
1.3 Hz, H-Ar), 7.28 (1H, d, J ¼ 4.6 Hz, H-Ar), 7.29 (1H, brs, H-Ar).
5m: IR (KBr): nmax ¼ 3416, 3314, 2950, 1691, 1656 cm21
.
1H NMR
(CDCl3): d ¼ 1.0 (3H, s, Me), 1.13 (3H, s, Me), 2.20 (1H, d, J ¼ 16.0 Hz,
H-6), 2.26 (1H, d, J ¼ 16.0 Hz, H-60), 2.45 (2H, brs, CH2), 3.64 (3H, s,
OMe), 3.79 (3H, s, OMe), 4.71 (1H, s, H-4), 6.17 (2H, brs, NH2), 6.79 (2H,
d, J ¼ 8.7 Hz, H-Ar), 7.21 (2H, d, J ¼ 8.7 Hz, H-Ar).
1
5n: IR (KBr): nmax ¼ 3412, 3304, 2959, 1693, 1655, 1614 cm21. H NMR
(CDCl3): d ¼ 1.01 (3H, s, Me), 1.13 (3H, s, Me), 2.19 (1H, d, J ¼ 16.0 Hz,
H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.30 (3H, s, Me), 2.46 (2H, brs,
CH2), 3.64 (3H, s, OMe), 4.72 (1H, s, H-4), 6.19 (2H, brs, NH2), 7.05 (2H,
d, J ¼ 7.90 Hz, H-Ar), 7.18 (2H, d, J ¼ 7.90 Hz, H-Ar).
5o: IR (KBr): nmax ¼ 3409, 3294, 2981, 1692, 1655 cm21. 1H NMR (CDCl3):
d ¼ 1.02 (3H, s, Me), 1.13 (3H, s, Me), 1.23 (3H, t, J ¼ 7.11 Hz, Me), 2.20
(1H, d, J ¼ 16.0 Hz, H-6), 2.27 (1H, d, J ¼ 16.0 Hz, H-60), 2.30 (3H, s,
Me), 2.46 (2H, brs, CH2), 4.09 (2H, m, OCH2), 4.71 (1H, s, H-4), 6.17 (2H,
brs, NH2), 7.04 (2H, d, J ¼ 7.90 Hz, H-Ar), 7.18 (2H, d, J ¼ 7.90 Hz, H-Ar).
5p: IR (KBr): nmax ¼ 3431, 3315, 1696, 1656, 1619 cm21. 1H NMR (CDCl3):
d ¼ 0.98 (3H, s, Me), 1.12 (3H, s, Me), 2.16 (1H, d, J ¼ 16.0 Hz, H-6), 2.26
(1H, d, J ¼ 16.0 Hz, H-60), 2.48 (2H, brs, CH2), 3.60 (3H, s, OMe), 4.80 (1H,
s, H-4), 6.30 (2H, brs, NH2), 7.39 (1H, t, J ¼ 13 Hz, H-Ar), 7.68 (2H, dt,
J ¼ 13.0, 3.15 Hz, H-Ar), 8.0 (1H, m, H-Ar), 8.08 (1H, t, J ¼ 3.15 Hz,
H-Ar), 8.13 (1H, brs, H-Ar).
5q: IR (KBr): nmax ¼ 3438, 3328, 2961, 1686, 1525 cm21. 1H NMR (CDCl3):
d ¼ 1.03 (3H, s, Me), 1.16 (3H, s, Me), 1.19 (3H, t, J ¼ 7.1 Hz, Me), 2.21 (1H,
d, J ¼ 16.0 Hz, H-6), 2.28 (1H, d, J ¼ 16.0 Hz, H-60), 2.51 (2H, brs, CH2),

1106
S. Balalaie et al.
4.07 (2H, m, OCH2), 4.85 (1H, s, H-4), 6.28 (2H, brs, NH2), 7.40 (1H, t,
J ¼ 7.90 Hz, H-Ar), 7.68 (1H, d, J ¼ 7.90 Hz, H-Ar), 8.0 (1H, d,
J ¼ 7.90 Hz, H-Ar).
5r: IR (KBr): nmax ¼ 3475, 3339, 1687, 1656, 1622 cm21. 1H NMR (CDCl3):
d ¼ 1.0 (3H, s, Me), 1.15 (3H, s, Me), 2.19 (1H, d, J ¼ 16.0 Hz, H-6), 2.28
(1H, d, J ¼ 16.0 Hz, H-60), 2.47 (1H, d, J ¼ 18 Hz, H-8), 2.52 (1H, d,
J ¼ 18 Hz, H-80), 3.64 (3H, s, OMe), 4.83 (1H, s, H-4), 6.32 (2H, brs,
NH2), 7.48 (2H, d, J ¼ 8.6 Hz, H-Ar), 8.12 (2H, d, J ¼ 8.60 Hz, H-Ar).
5s: IR (KBr): nmax ¼ 3476, 3338, 1687, 1659, cm21
.
1H NMR
(CDCl3):d ¼ 1.0 (3H, s, Me), 1.15 (3H, s, Me), 1.17 (3H, t, J ¼ 7.1 Hz,
Me), 2.20 (1H, d, J ¼ 16.0 Hz, H-6), 2.28 (1H, d, J ¼ 16.0 Hz, H-60), 2.49
(1H, d, J ¼ 16.0 Hz, H-8), 2.50 (1H, d, J ¼ 16.0 Hz, H-80), 4.06 (2H, m,
OCH2), 4.83 (1H, s, H-4), 6.32 (2H, brs, NH2), 7.48 (2H, d, J ¼ 8.8 Hz,
H-Ar), 8.12 (2H, d, J ¼ 8.8 Hz, H-Ar).
ACKNOWLEDGMENTS
Saeed Balalaie is grateful to the Alexander von Humboldt foundation for the
research fellowship and equipment donation. Partial support of this work by
the K. N. Toosi University of Technology Research Council is gratefully
acknowledged.
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