Synthesis of [Zn(II)BHPPDAH] as new heterogeneous catalyst without being immobilized on any support and applied for mannich reaction

Article abstract of DOI:10.1002/hc.21103

In this paper, a novel heterogeneous complex of zinc with N,N-bis(2-hydroxyphenyl)pyridine-2,6-dicarboxamide(BHPPDAH) was synthesized. The catalyst was found to be a highly effective catalyst for the three-component coupling reactions of aldehydes, alkynes, and amines (A3 coupling) via C-H activation. The reactions could be applied to both aromatic and aliphatic aldehydes and alkynes. Nearly quantitative yields of the desired products were obtained in most cases. The reaction proceeds without any cocatalyst or activator, and water is the only byproduct. The catalyst was quantitatively recovered from the reaction by a simple filtration and reused for five cycles with almost consistent activity.

Full text of DOI:10.1002/hc.21103

Heteroatom Chemistry
Volume 24, Number 5, 2013
Synthesis of [Zn(II)BHPPDAH] as New
Heterogeneous Catalyst without Being
Immobilized on Any Support and Applied
for Mannich Reaction
Reza Khalifeh,1 Hashem Sharghi,2 and Zahra Rashidi2
1Department of Chemistry, Shiraz University of Technology, Shiraz 71555–313, Iran
2Department of Chemistry, College of Science, Shiraz University, Shiraz 71454, Iran
Received 31 October 2012; revised 7 May 2013
an alkyne, and an amine (A3 coupling) is one of the
best examples [2]. The resultant propargylamines,
obtained by the A3-coupling reaction, are an attrac-
tive class of compounds owing to their variety of bi-
ological activities such as being enzyme inhibitors,
antitumor, antibiotics, herbicides, and pharmaceu-
tical agents [3]. In addition, they are useful interme-
diates in organic synthesis chemistry and important
structural elements of natural products [4]. There
are several transition-metal catalysts able to carry
out A3-coupling reaction via C–H activation. These
include iridinum [5a], copper [5b, 5c, 5d], silver [5e],
gold [5f], and zinc [5g].
To improve the recovery for reusing, catalyst
species have been immobilized on various supports
such as hydroxyapatite [6], layered double hydroxide
[7], 12-tungstophosphoric acid [8], alumina [9], sil-
ica [10], and zeolites [11]. These heterogeneous cat-
alysts three-component Mannich reactions require
functional groups to be immobilized on a support.
The development of heterogeneous catalyst for
the production of fine chemicals in industrial pro-
cesses, which helps to minimize the problems of in-
dustrial disposal and waste treatment, remains an
active research area because heterogeneous catalyst
is easy to separate, potentially reusable, and envi-
ronmentally acceptable. Thus, the development of
highly efficient, simple in handling, stable, easy in
removal from the reaction mixture, and subsequent
reusable heterogeneous catalytic system is desirable
for the preparation of propargylamines through the
ABSTRACT: In this paper,
a novel heteroge-
neous complex of zinc with N,N-bis(2-hydroxyphenyl)
pyridine-2,6-dicarboxamide(BHPPDAH) was synthe-
sized. The catalyst was found to be a highly ef-
fective catalyst for the three-component coupling
reactions of aldehydes, alkynes, and amines (A3
coupling) via C–H activation. The reactions could
be applied to both aromatic and aliphatic aldehydes
and alkynes. Nearly quantitative yields of the desired
products were obtained in most cases. The reaction
proceeds without any cocatalyst or activator, and
water is the only byproduct. The catalyst was quanti-
tatively recovered from the reaction by a simple filtra-
tion and reused for five cycles with almost consistent
ꢀC
activity. 2013 Wiley Periodicals, Inc. Heteroatom
Chem. 24:372–383, 2013; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21103
INTRODUCTION
Multicomponent coupling reactions have attracted
much attention in organic synthesis. In view of this,
they have been applied as a powerful synthetic tool
to access complex structures from simple precur-
sors [1]. Three-component coupling of an aldehyde,
Correspondence to: Reza Khalifeh; e-mail: khalifeh@sutech.ac.ir
and Hashem Sharghi; e-mail: shashem@susc.ac.ir.
ꢀC
2013 Wiley Periodicals, Inc.
372

Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 373
SCHEME 1 Preparation of heterogeneous catalyst.
SCHEME 2 Mannich reaction of a model compound in the presence of heterogeneous catalyst.
classic Mannich reaction. Inspired by these devel-
opments, and as a part of our program aiming to
develop selective and environment-friendly methods
for the preparation of fine chemicals and in the con-
tinuation of our studies to utilize heterogeneous cat-
alysts for the synthesis of organic compounds [12],
we report the synthesis of a series of new metal com-
plexes. We also illustrate its application as an ex-
cellent heterogeneous catalyst for the synthesis of
propargylamines without any cocatalyst, activator,
or base under mild conditions. The catalyst shows a
high catalytic activity and the reactions generate the
corresponding products in nearly quantitative yields
in most cases. In addition, easy catalyst recovery and
excellent recycling efficiency of the catalyst make it
an ideal catalyst for Mannich reactions.
To optimize the reaction conditions, the con-
densation of morpholine (1 mmol), formalin (37%,
0.4 mL), and phenylacetylene (1 mmol) was stud-
ied as a model reaction to provide propargylamines
(Scheme 2).
A variety of reaction parameters were screened
for this reaction. The results are presented in Table 1.
The condensation reaction of phenylacetylene, mor-
pholine, and formalin in the absence of the catalyst
led to a very small amount of product. Increasing the
temperature from 30◦C to 70◦C improved the conver-
sion (Table 1, entries 2), whereas on further increas-
ing the temperature to 100◦C, no such improvement
in the conversion was obtained. A positive influence
of catalyst on the Mannich reaction is known. In an
effort to develop a better catalytic system, we exam-
ined the synthesis of the corresponding propargy-
lamine of model compound by several metal com-
plexes catalysis. Six different metallic ions were
tested. Among the metal-incorporated catalysts ex-
amined, the use of Zn(II)-complex in the presence of
water as solvent gave the best result in terms of yield.
According to Table 1, use of complexes of Cu(II)
and Cd(II) also gave good yields (Table 1, entries
7, 8). We use Zn(II)-complex because Zn is a cheap
and available metal. In the next step, we focused our
attention to investigate the effect of temperature uti-
lizing [Zn(II)BHPPDAH] (2.0 mol%) on our model
RESULTS AND DISCUSSION
The reaction path way for the preparation of the cat-
alyst is indicated in Scheme 1 Fortunately, due to
insolubility of the different metal complexes in all
common solvents, they could be applied as hetero-
geneous catalysts without being immobilized on a
support.
To explore the catalytic activity, the Mannich re-
action of secondary amines, aldehydes, and alkynes
was conducted with the present catalysts.
Heteroatom Chemistry DOI 10.1002/hc

374 Khalifeh, Sharghi, and Rashidi
TABLE 1 Mannich Reaction of Phenylacetylen(1mmol), Morpholin(1mmol), and Formalin(0.4 mL) under Various Conditions
Entry
Catalyst (mol%)
_____
_____
BHPPDAH
Temperature
Solvent
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
r.t.
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
EtOH
THF
Dioxane
DMSO
DMF
Toluene
CH3CN
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
r.t.
10
10
40
30
40
85
90
35
95
95
60
45
70
85
50
25
10
70
[Co(BHPPDAH)] (2)
[Fe(BHPPDAH)] (2)
[Mn(BHPPDAH)] (2)
[Cd(BHPPDAH)] (2)
[Cu(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (5)
[Zn(BHPPDAH)] (1)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
[Zn(BHPPDAH)] (2)
9
10
11
12
13
14
15
16
17
18
19
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
70◦C
r.t., room temperature.
reaction (Table 2, enteries 9, 10). Preliminary inves-
tigations showed that the rate of the reaction was
significantly affected by the temperature of the reac-
tion and a remarkable increase in yield was observed
at 70◦C compared to the various temperatures. Fur-
ther increases in temperature did not have any in-
fluence on the yield and time. During the course
of our further optimization of the reaction condi-
tions, we found that the loading levels of the catalyst
[Zn(II)BHPPDAH] also have an effect on the yield. In
the absence of catalyst, the reaction gave only a small
amount of product even after 5 h (Table 1, entry 2).
In addition, the model reaction with ligand was ex-
amined and the results show that in the absence of
metal, the reaction does not proceed to good yield
(Table 1, entry 3). When using 2 mol% loading of new
heterogeneous Zn(II)-complex, the reaction was gen-
erally completed and the best result was obtained.
Increasing the catalyst amount neither enhanced the
yield nor lowered the reaction time significantly,
while decreasing the catalyst amount reduced the
yield of the product. (Table 1, entries 11, 12).
Also, to determine the most suitable reaction
conditions, we focused our attention to the ef-
fect of solvents on the model reaction using the
optimized amount of catalysts [Zn(II)BHPPDAH].
Various solvents were examined and it was
found that the solvent plays a significant role in
terms of isolated yield. Among various solvents
tested, ethanol and dimethyl sulfoxide (DMSO)
gave moderate yields of the expected product
(Table 1, entries 13 and 16). Acetonitrile and tetrahy-
drofuran afforded the product in good yields (Ta-
ble 1, entries 14 and 19). Water clearly stands out
as a solvent of choice with its high yield, cheap-
ness, green character, and environmental acceptabil-
ity. Thus, careful analysis of the optimized reactions
revealed that the optimum conditions for this one-
pot procedure are the addition of phenylacetylene
(1 mmol) to a solution of morpholine (1 mmol) and
formalin (37%) (0.4 mL) in the presence of 2 mol%
of Zn complex at 70◦C for 2 h. By using this reaction
conditions, we were able to prepare the correspond-
ing propargylamine in 95% yield.
To the best of our knowledge, this is the first ex-
ample of catalytic synthesis of propargylamines us-
ing a heterogeneous complex of Zn(II) in a catalytic
amount without being immobilized on any support,
in the absence of base in water. In addition, no ad-
ditives were needed for this system and the experi-
mental process was quite simple and easy. A variety
of amines and alkynes bearing different functional
groups were employed as the reaction substrates to
explore the scope and generality for the catalyst ap-
plication. All the results are summarized in Table 2.
Various amines and aldehydes were found to re-
act with phenylacetylene in the presence of a cat-
alytic amount of heterogeneous [Zn(II)BHPPDAH]
to give the corresponding propargylamines in good
to excellent yields. In the next step, we decided
to study the reaction of several terminal aliphatic
alkynes and amines with formalin in the presence of
catalysts under optimized conditions. (Table 2, en-
tries 2–4, 15).
As depicted in Table 2, aromatic aldehydes,
including those bearing functional groups, such
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Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 375
TABLE 2 Synthesis of Mannich-Type Reaction from Various Secondary Amines (1.0 mmol), Terminal Alkynes (1.0 mmol),
and Aldehydes (1.0 mmol) in the Presence of Heterogeneous [Zn(II)BHPPDAH] (2.0 mol%) in Water at 70◦C by Way of a
Three-Component Reaction
Entry
Amine
Aldehyde
Alkyne
Product
Time (h)
Yield (%)a
1
CH2O
1.5
95
2
CH2O
2
85
3
CH2O
4
70
4
CH2O
2
90
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

376 Khalifeh, Sharghi, and Rashidi
TABLE 2 Continued
Entry
Amine
Aldehyde
Alkyne
Product
Time (h)
Yield (%)a
5
6
7
10
10
10
89b
85b
92b
8
6
85
9
3
75c
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 377
TABLE 2 Continued
Entry
Amine
Aldehyde
Alkyne
Product
Time (h)
Yield (%)a
10
11
CH2O
1.5
1.5
95
90
CH2O
12
13
CH2O
1.5
95
CH2O
5
70c
14
CH2O
5.5
70c
15
CH2O
2
85
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

378 Khalifeh, Sharghi, and Rashidi
TABLE 2 Continued
Entry Amine
Aldehyde Alkyne
Product
Time (h) Yield (%)a
16
CH2O
4
80
17
CH2O
8
70
aIsolated yield.
bThe reaction was performed at 100◦C.
cThe reaction was performed at 80◦C.
as methyl and chloro substitutions, were able to un-
dergo the corresponding three-component coupling
reaction. Aryl aldehyde with electron-withdrawing
group, such as chloro, reacted smoothly; however,
it seems that electron-donating group bound to the
benzene ring, such as methyl, could reduce the reac-
tivity (Table 2, entries 6, 7).
In an attempt to broaden the scope of our
methodology, the possibility of performing the re-
action with a heterocyclic aldehyde instead of
aromatic aldehyde was also investigated. In this
way, thiophene-2-carbaldehyde was reacted with
phenylacetylene and morpholine in the presence of
[Zn(II)BHPPDAH] at 70◦C for 6 h to afford the ex-
pected product in 85% yield (Table 2, entry 8).
In addition to aromatic aldehydes, aliphatic
aldehydes such as pantanal afforded the correspond-
ing propargylic amines in good yields without any
trimerization (Table 2, entry 9).
yields, respectively (Table 2, entry 10, 11). In a sim-
ilar manner, the reaction of 2-phenyl-N-benzyl ethyl
amine with formalin and phenylacetylene catalyzed
by [Zn(II)BHPPDAH] at 80◦C for 5.5 h produced cor-
responding propargylamine in 70% yield (Table 2,
entry 14).
After this study, which showed the broad scope
of the reaction, we turned our attention to the ster-
ically hindered amines. For this purpose, we chose
azacrown ether as a substrate. The coupling of aza-
crown ether, formalin, and phenylacetylene pro-
ceeded smoothly to afford the corresponding propar-
gylamine in high yield under standard conditions
(Table 2, entries 16, 17).
The results in Table 2 indicate that the aromatic
aldehydes were able to undergo the A3 coupling.
However, the reaction was found to be strongly influ-
enced by the nature of the aldehyde. The use of aro-
matic aldehydes gave lower conversions and lower
yields. Aliphatic aldehydes, on the other hand, dis-
played higher reactivity and cleaner reactions.
To access the feasibility of applying this method
in a preparative scale, we carried out the reaction
of morpholin, phenylacetylene, and formalin on a
30-mmol scale in the presence of the heterogeneous
Different amines also have an effect on the
reaction; besides the fact that dialkylamines re-
acted smoothly in these conditions. Diethylamine
and dibutylamine were reacted with phenylacety-
lene under the influence of the catalyst to pro-
duce the corresponding product in 95% and 90%
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 379
TABLE 3 Investigation of Catalyst Recyclability by Reaction
mination of the substrates and reaction monitoring
were accomplished by thin layer chromatography
on silica gel PolyGram SILG/UV 254 plates. Column
chromatography was carried out on short columns
of silica gel 60 (70–230 mesh) in glass columns (2–
3 cm diameter) using 15–30 g silica gel per 1 g of
crude mixture. Chemical materials were either pre-
pared in our laboratories or were purchased from
Fluka, Aldrich, and Merck.
between Phenylacetylene, Morpholine, and Formalin in Water
Number of Uses
Yield (%)
Recovery of Catalyst (%)
1
2
3
4
5
95
95
90
85
85
98
95
95
93
90
catalyst (Table 2, entry 1). As expected, the reaction
proceeded similar to the case on a smaller scale, and
the desired propargylamine was obtained in 89% iso-
lated yield in 2 h.
Synthesis of N,N-bis(2-Hydroxyphenyl)pyridine-
2,6-dicarboxamide(BHPPDAH)
2,6-Pyridinedicarboxylic acid (1 mmol) was boiled
under reflux in SOCl2 for 4 h. Excess of SOCl2 was re-
moved under reduced pressure to leave 2,6-pyridine
dicarbonyldichloride. Then amine (2 mmol) was dis-
solved in dry methylene chloride (10 mmol) followed
by triethylamine (2 mmol). After that 2,6-pyridine di-
carbonyldichloride (1 mmol) was dropwise added to
the above solution at 0◦C and the reaction mixture
was stirred for 2 h. Then the precipitate was washed
with a saturated solution of NaHCO3. The product
was recrystallized from aqueous ethanol (50%) for
further purification.
From an environmental point of view, it is de-
sirable to minimize the amount of waste for each
organic transformation. In this context, the catalyst
was recycled for subsequent runs. The recyclability
of the catalyst was investigated using a model reac-
tion between phenylacetylene, morpholine, and for-
malin in the presence of 2 mol% of the catalyst. After
the completion of the reaction, the mixture was fil-
tered to separate the catalyst. The recycled catalyst
was used for further runs, and it was found that its
activity does not show any significant decrease after
five runs (Table 3). Leaching experiment showed that
the catalytic activity of [Zn(II)BHPPDAH] remained
largely unchanged for five successive runs.
In conclusion, we have successfully developed
an efficient protocol using Zn(II)-complex as a new
heterogeneous catalyst for the one-pot synthesis of
diverse propargylamines, for the first time, in moder-
ate to excellent yields. The catalyst could be readily
recovered and reused, thus making this procedure
more environmentally acceptable while no catalyst
leaching was observed.
N,N-bis(2-Hydroxyphenyl)pyridine-2,6-
dicarboxamide [12i]
Yellowish solid; yield 95%, melting point: 222–
224◦C. IR (KBr): 3336 (NH), 3190 (OH), 1670 (C=O),
1597, 1543, 1458, 748 cm−1 1H NMR (DMSO,
.
250 MHz) δ = 6.82–7.06 (m, 6H), 7.99 (d, 2H,
J = 7.9 Hz), 8.26–8.39 (m, 3H), 10.02 (s, 2H), 10.41
(s, 2H). 13C NMR (DMSO, 62.9 MHz) δ = 115.3,
119.1, 122.2, 124.9, 125.3, 125.4, 140.2, 148.5, 148.8,
160.9. Mass (m/z) (%): 351 (M+ +2, 30.4), 350 (M+
+1, 95.8), 349 (M+, 94.8), 348 (44.9), 332 (28.7),
304 (22.8), 286 (17.7), 241 (25.5), 213 (44.4), 187
(74.9), 149 (19.6), 129 (23.1), 97 (36.3), 80 (46.7), 57
(100). Anal. Calcd. for C19H15N3O4: C, 65.32; H, 4.33.
Found: C, 65.18; H, 4.48.
EXPERIMENTAL
Instrumentation, Analyses, and Starting
Materials
Nuclear magnetic resonance (NMR) spectra were
recorded on a Bruker Avance DPX-250 (1H NMR
at 250 MHz and 13C NMR at 62.9 MHz) spectrom-
eter in pure deuterated solvents with tetramethylsi-
lane as an internal standard. Infrared (IR) spectra
were obtained using a Shimadzu Fourier transform
IR 8300 spectrophotometer. Mass spectra were
determined on a Shimadzu GCMS-QP 1000 EX in-
struments at 70 or 20 ev. Melting points (mp) were
determined in open capillary tubes in a Bu¨chi-535
circulating oil melting point apparatus. Elemental
analyses were performed on a Thermo Finnigan
CHNS–O analyzer, 1112 series. The purity deter-
Synthesis of [M(BHPPDAH)H2O]
Complexes [12i]
BHPPDAH (1 mmol) was boiled under reflux with
NaOH (2 mmol) in 75% aq/EtOH (1 mL) for 30 min.
The metal(II) salt (1 mmol) dissolved in EtOH was
added and the mixture was refluxed further for 2 h.
EtOH was then removed under reduced pressure to
leave a precipitate, which was filtered, washed with
H2O, and dried in air, which afforded 98% of brown
solid of [M(BHPPDAH)H2O].
Heteroatom Chemistry DOI 10.1002/hc

380 Khalifeh, Sharghi, and Rashidi
[Zn(BHPPDAH)H2O]Complexes
4-Methyl-7,8-bis{[4-(4-morpholinyl)-2-
butynyl]oxy}-2H-chromen-2-one (3)
Due to the poor solubility of the complex in DMSO-
d6 and other solvents, we could not characterize the
complex by NMR spectroscopy. Brown solid; yield
98%. IR (KBr): 3341(NH), 1665(C=O), 1593, 1535,
Brown oil; IR (neat): 748(w), 856(w), 1003(m),
1080(m), 1111(m), 1288(m), 1599(m), 1728(s),
2117(w), 2854(m) cm−1. 1H NMR (CDCl3, 250 MHz)
δ = 2.29 (t, 4H, J = 4.2 Hz), 2.33 (s, 3H), 2.43 (t,
4H, J = 4.5 Hz), 3.18 (s, 2H), 3.24 (s, 2H), 3.56 (t, 4H,
J = 4.8 Hz), 3.63 (t, 4H, J = 4.8 Hz), 4.83 (s, 2H), 4.86
(s, 2H), 6.09 (s, 1H), 6.96 (d, 1H, J = 9.0 Hz), 7.26
(d, 1H, J = 8.8 Hz). 13C NMR (CDCl3, 62.9 MHz) δ =
18.6, 47.1, 47.2, 51.7, 52.0, 57.2, 60.6, 66.5, 79.4, 80.3,
82.4, 83.2, 110.1, 112.4, 115.2, 119.8, 133.9, 148.0,
152.6, 153.5, 160.1. Anal. Calcd. for C26H30N2O6
(466.530): C, 66.94; H, 6.48. Found: C, 67.06; H, 6.59.
1455, 745 cm−1
.
General Procedure for Mannich Condensation of
Terminal Alkynes with Amines and Aldehyde
[Zn(II) BHPPDAH] (0.009 g) (2 mol%) [12i] was
added to a mixture of secondary amine (1.0 mmol),
terminal alkyne (1.0 mmol), aldehyde (1.0 mmol),
and water (2 mL) in a round-bottomed flask and
stirred for the indicated time at 70◦C. After the re-
action was completed and the solution was cooled
to the room temperature, ethyl acetate was added
and the slurry was stirred at room temperature
to ensure product removal from the surface. The
mixture was filtered and the aqueous layers were
extracted with ethyl acetate and concentrated to
give the crude product, which was further puri-
fied by column chromatography to yield the desired
propargylamine.
4-[4-(4-Chloro-2-nitrophenoxy)-2-butynyl]
morpholine (4)
White powder; mp 96◦C–97◦C; IR (KBr): 679(s),
810(s), 879(s), 987(s), 1111(s), 1234(m), 1273(m),
1358(s), 1481(m), 1527(s), 1605(m), 2190(w),
2855(m) cm−1. 1H NMR (CDCl3, 250 MHz) δ = 2.48
(t, 4H, J = 4.3 Hz), 3.3 (s, 2H), 3.70 (t, 4H, J = 4.5 Hz),
4.87 (s, 2H), 7.19 (d, 1H, J = 7.5 Hz), 7.49 (d, 1H, J =
9.0 Hz), 7.84 (s, 1H). 13C NMR (CDCl3, 62.9 MHz) δ =
47.3, 52.2, 57.9, 66.7, 78.4, 84.5, 116.9, 125.6, 126.2,
133.7, 140.5, 149.5. Anal. Calcd. for C14H15ClN2O4
(310.735): C, 54.11; H, 4.87. Found: C, 53.99; H, 4.90.
4-(3-Phenyl-2-propynyl)morpholine (1) [12f]
Brown oil; IR (neat): 694(s), 760(s), 860(s), 910(w),
1007(m), 1072(m), 1115(s), 1238(m), 1450(s),
4-(1,3-Diphenyl-2-propynyl)morpholine
(5) [12a]
1716(s), 2858(s), 2932(s) cm−1 1H NMR (CDCl3,
.
250 MHz): δ = 2.63 (t, 4H, J = 4.6 Hz), 3.48
(s, 2H), 3.74 (t, 4H, J = 4.5 Hz), 7.25–7.42 (m, 5H). 13C
NMR (CDCl3, 62.9 MHz): δ = 47.7, 52.1, 66.5, 83.7,
85.7, 122.8, 128.2, 131.6. Anal. Calcd. for C13H15NO
(201.267): C, 77.58; H, 7.51. Found: C, 77.67; H, 7.39.
Yellow oil; IR (neat): 702(s), 748(m), 1111(s),
1281(s), 1450(m), 1697(s), 2118(w), 2858(m) cm−1
.
1H NMR (CDCl3, 250 MHz) δ = 2.67–2.71 (m, 4H),
3.76–3.82 (m, 4H), 4.85 (s, 1H), 7.36–7.46 (m, 5H),
7.57–7.61 (m, 3H), 7.69–7.73 (m, 2H). 13C NMR
(CDCl3, 62.9 MHz) δ = 50.0, 62.1, 67.2, 85.4, 88.8,
123.1, 127.9, 128.4, 128.5, 128.7, 129.7, 131.9, 138.1.
Mass m/z (%) 279 (2.5, M++2), 278 (13.1, M++1),
277 (28.9, M+), 191 (100.0), 86 (47.0), 56 (80.7). Anal.
Calcd. for C19H19NO (277.365): C, 82.28; H, 6.90.
Found: C, 82.17; H, 7.09.
5-Chloro-8-{[4-(4-morpholinyl)-2-butynyl]oxy}
quinoline (2)
Brown oil; IR (neat): 789(m), 1111(s), 1304(m),
1365(m), 1458(s), 1589(m), 2154(w), 2854(w) cm−1
.
1H NMR (CDCl3, 250 MHz) δ = 2.46 (t, 4H, J =
4.7 Hz), 3.27 (s, 2H), 3.66 (t, 4H, J = 4.7 Hz), 5.02
4-[1-(4-Methylphenyl)-3-phenyl-2-propynyl]
morpholine (6) [12a]
(s, 2H), 7.15 (d, 1H,
J
=
8.5 Hz), 7.51
(d, 1H,
J
=
3.2 Hz), 7.53 (t, 1H,
J
=
Yellow powder; mp 79◦C–80◦C; IR (KBr): 748(s),
1111(s), 1281(m), 1450(m), 2167(m), 2862(m),
2962(m) cm−1. 1H NMR (CDCl3, 250 MHz) δ = 2.40
(s, 3H), 2.65–2.70 (m, 4H), 3.76–3.79 (m, 4H), 4.79
(s, 1H), 7.22 (d, 2H, J = 7.9 Hz), 7.36 (dd, 2H, J1 =
6.5 Hz, J2 = 2.3 Hz), 7.52–7.58 (m, 5H). 13C NMR
(CDCl3, 62.9 MHz) δ = 21.2, 50.0, 61.9, 67.2, 85.6,
5.0 Hz), 8.51 (dd, 1H, J1
=
8.5 Hz,
J2 = 1.5 Hz), 8.95 (s, 1H). 13C NMR (CDCl3,
62.9 MHz) δ = 46.4, 51.2, 56.0, 65.4, 78.7, 82.2,
108.9, 121.4, 122.0, 125.1, 126.1, 132.0, 139.8, 148.8,
151.3. Anal. Calcd. for C17H17ClN2O2 (316.786): C,
64.46; H, 5.41. Found: C, 64.34; H, 5.53.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 381
88.5, 123.2, 128.3, 128.4, 128.6, 129.1, 131.9, 135.1,
137.4. Mass m/z (%) 293 (5.3, M++2), 292 (15.1,
M++1), 291 (24.8, M+), 233 (24.5), 205 (100.0), 149
(14.2), 86 (30.5), 56 (48.7). Anal. Calcd. for C20H21NO
(291.392): C, 82.44; H, 7.26. Found: C, 82.36; H, 7.39.
127.9, 131.6. Anal. Calcd. for C13H17N (187.284): C,
83.37; H, 9.15. Found: C, 83.52; H, 8.98.
N,N-Dibutyl-3-phenyl-2-propyn-1-amine
(11) [12f]
Brown oil; IR (neat): 690(s), 756(s), 910(m),
1092(m), 1323(w), 1377(w), 1466(m), 1678(w),
4-[1-(4-Chlorophenyl)-3-phenyl-2-propynyl]
morpholine (7)
1
2226(w), 2816(m), 2866(s), 2932(s) cm−1. H NMR
(CDCl3, 250 MHz) δ = 0.93 (t, 6H, J = 7.2 Hz), 1.22–
1.55 (m, 8H), 2.54 (t, 4H, J = 7.2 Hz), 3.62 (s, 2H),
7.24–7.68 (m, 5H). 13C NMR (CDCl3, 62.9 MHz) δ =
14.0, 20.7, 29.7, 42.6, 53.5, 84.6, 84.9, 123.4, 127.8,
128.1, 131.4. Anal. Calcd. for C17H25N (243.391): C,
83.89; H, 10.35. Found: C, 83.98; H, 10.17.
Brown oil; IR (neat): 748(s), 995(m), 1111(s),
1281(m), 1597(m), 1674(m), 2141(w), 2823(m),
2939(m) cm−1. 1H NMR (CDCl3, 250 MHz) δ = 2.47
(t, 4H, J = 4.5 Hz), 3.58 (t, 4H, J = 3.8 Hz), 4.61
(s, 1H), 7.17–7.21 (m, 5H), 7.36–7.46 (m, 4H). 13C
NMR (CDCl3, 62.9 MHz) δ = 49.8, 61.4, 66.9, 84.4,
88.9, 122.7, 128.9, 129.9, 131.9, 133.6, 136.5. Anal.
Calcd. for C19H18ClNO (311.810): C, 73.19; H, 5.82.
Found: C, 73.24; H, 5.93.
2,2’-(3-Phenyl-2-propynylazanediyl)diethanol
(12) [12f]
Yellow oil; IR (neat): 760(w), 1072(s), 1048(m),
1570(m), 1655(m), 2878(m), 2943(m), 3356(br)
4-[3-Phenyl-1-(3-thienyl)-2-propynyl]
morpholine (8)
1
cm−1. H NMR (CDCl3, 250 MHz): δ = 2.78 (t, 4H,
J = 5.3 Hz), 3.56–3.71 (m, 6H), 4.37 (s, 2H), 7.26–
7.40 (m, 5H). 13C NMR (CDCl3, 62.9 MHz) δ = 50.6,
55.3, 58.7, 59.6, 83.9, 85.3, 122.8, 128.1, 128.2, 131.6.
Anal. Calcd. for C13H17NO2 (219.282): C, 71.21; H,
7.81. Found: C, 71.36; H, 7.68.
Brown oil; IR (neat): 756(m), 1003(w), 1119(s),
1281(m), 1443(m), 1736(s), 2130(w), 2855(s),
2955(s) cm−1
.
1H NMR (CDCl3, 250 MHz) δ =
2.48–2.50 (m, 4H), 3.57–3.59 (m, 4H), 4.68 (d, 1H,
J = 3.5 Hz), 7.11–7.39 (m, 8H). 13C NMR (CDCl3,
62.9 MHz) δ = 49.7, 57.8, 67.1, 85.3, 87.3, 122.9,
123.7, 125.8, 127.7, 128.3, 128.4, 131.8, 139.5. Anal.
Calcd. for C17H17NOS (283.387): C, 72.05; H, 6.05.
Found: C, 72.14; H, 6.12.
N-Benzyl-N-ethyl-3-phenyl-2-propyn-1-amine
(13) [12f]
Brown oil; IR (neat): 694(s), 756(s), 787(s), 1053(w),
1099(w), 1130(w), 1323(m), 1454(m), 1489(m),
1597(w), 2361(w), 2820(m), 2932(m), 2970(m),
4-(1-Butyl-3-phenyl-2-propynyl)morpholine (9)
3028(w) cm−1
.
1H NMR (CDCl3, 250 MHz) δ =
Yellow oil; IR (neat): 748(s), 1003(m), 1119(s),
1.04 (t, 3H, J = 7.2 Hz), 2.56 (q, 2H, J = 7.2 Hz),
3.42 (s, 2H), 3.58(s, 2H), 7.04–7.37 (m, 10H). 13C
NMR (CDCl3, 62.9 MHz) δ = 13.1, 41.9, 58.4, 84.7,
85.8, 123.7, 127.3, 127.6, 128.5, 129.4, 131.9, 139.1.
Anal. Calcd. for C18H19N (249.355): C, 86.70; H, 7.68.
Found: C, 86.87; H, 7.81.
1458(m), 1728(m), 2240(m), 2854(s), 2955(s) cm−1
.
1H NMR (CDCl3, 250 MHz) δ = 0.85 (t, 4H, J =
7.0 Hz), 1.18–1.34 (m, 3H), 1.59–1.65 (m, 2H), 2.48–
2.65 (m, 4H), 3.40 (t, 1H, J = 7.5 Hz), 3.64–3.69 (m,
4H), 7.19–7.22 (m, 3H), 7.33–7.37 (m, 2H). 13C NMR
(CDCl3, 62.9 MHz) δ = 14.0, 22.4, 28.8, 32.6, 49.7,
58.1, 67.1, 86.1, 87.1, 123.2, 128.0, 128.6, 131.7. Anal.
Calcd. for C17H23NOS (257.374): C, 79.33; H, 9.01.
Found: C, 79.21; H, 8.89.
N-Benzyl-3-phenyl-N-(2-phenylethyl)-2-propyn-
1-amine (14) [12f]
Brown oil; IR (neat): 694(s), 756(s), 1030(w),
1072(w), 1119(m), 1323(m), 1454(s), 1493(s),
1601(m), 2361(w), 2824(m), 2932(m), 3028(m),
N,N-Diethyl-3-phenyl-2-propyn-1-amine
(10) [12f]
3059(m) cm−1
.
1H NMR (CDCl3, 250 MHz) δ =
Brown oil; IR (neat): 690(s), 756(s), 1068(m),
1319(m), 1381(w), 1489(m), 1597(w), 2338(w),
2820(m), 2935(s) cm−1. 1H NMR (CDCl3, 250 MHz):
δ = 0.98 (t, 6H, J = 7.1 Hz), 2.44 (q, 4H, J = 7.1 Hz),
3.49 (s, 2H), 7.11–7.31 (m, 5H). 13C NMR (CDCl3,
62.9 MHz) δ = 12.6, 41.8, 47.2, 84.3, 84.9, 127.4,
2.80 (s, 4H), 3.52 (s, 2H), 3.68 (s, 2H), 7.08–7.38
(m, 15H). 13C NMR (CDCl3, 62.9 MHz) δ = 34.5,
42.6, 55.6, 58.4, 84.8, 86.0, 123.7, 126.3, 127.7, 128.3,
128.8, 129.4, 129.9, 132.0, 139.0, 140.6. Anal. Calcd.
for C24H23N (325.452): C, 88.57; H, 7.12. Found: C,
88.71; H, 6.97.
Heteroatom Chemistry DOI 10.1002/hc

382 Khalifeh, Sharghi, and Rashidi
REFERENCES
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δ = 0.93–0.99 (m, 6H), 2.42–2.45 (m, 4H), 3.39
(s, 2H), 5.00 (s, 2H), 7.15 (d, 1H, J = 8.5 Hz), 7.47–
7.52 (m, 2H), 8.46–8.49 (m, 1H), 8.92 (s, 1H). 13C
NMR (CDCl3, 62.9 MHz) δ = 12.3, 40.7, 47.1, 57.1,
79.1, 83.1, 110.0, 122.3, 122.9, 126.1, 127.0, 132.9,
140.9, 149.8, 152.3. Anal. Calcd. for C17H19ClN2O
(302.802): C, 67.43; H, 6.32. Found: C, 67.52; H, 6.24.
7-(3-Phenyl-2-propynyl)-5,6,7,8,9,10-hexahydro-
2H-1,13,4,7,10-benzodioxatriazacyclopentade-
cine-3,11(4H,12H)-dione (16) [12f]
White powder; mp: 185(C–186(C. IR (KBr): 571(w),
689(w), 756(s), 818(m), 1045(m), 1126(m), 1215(m),
1261(s), 1323(w), 1435(m), 1508(s), 1686(vs),
2338(w), 2847(w), 2905(w), 3410(s) cm−1. H NMR
1
[5] (a) Sakaguchi, S.; Mizuta, T.; Furuwan, M.; Kubo, T.;
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(CDCl3, 250 MHz) δ = 2.59–2.63 (m, 4H), 3.54–
3.61 (m, 4H), 3.68 (s, 2H), 4.49 (s, 4H), 6.85–7.02
(m, 4H), 7.28–7.45 (m, 5H), 7.51 (s, 2H). 13C NMR
(CDCl3, 62.9 MHz) δ = 35.1, 37.5, 47.4, 51.6, 52.3,
66.7, 77.6, 80.9, 112.3, 122.0, 146.0, 167.2. Mass m/z
(%) 409 (M++2, 0.8), 408 (M++1, 3.3), 407 (M+,
4.4), 337(0.8), 307(0.9), 294(0.2), 293(0.4), 292(0.9),
251(1.0), 183(12.1), 156(25.3), 115(100), 85(71.4),
56(58.5). Anal. Calcd. for C23H25N3O4 (407.467): C,
67.80; H, 6.18. Found: C, 67.63; H, 6.34.
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7-{4-[(7-{[4-(3,11-Dioxo-3,4,5,6,9,10,11,12-
octahydro-2H-1,13,4,7,10-benzodioxatriaza-
cyclopentadecin-7(8H)-yl)-2-butynyl]oxy}-4-
methyl-2-oxo-2H-chromen-8-yl)oxy]-2-butynyl}-
5,6,7,8,9,10-hexahydro-2H-1,13,4,7,10-
benzodioxatriazacyclopentadecine-
3,11(4H,12H)-dione (17)
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White powder; mp 144◦C–146◦C; IR (KBr): 578(m),
756(m), 1088(s), 1257(s), 1504(s), 1604(m), 1674(s),
1728(s), 2114(w), 2847(m), 3232(m), 3402(s) cm−1
.
1H NMR (CDCl3, 250 MHz) δ: 2.41 (s, 3H), 2.61–2.68
(m, 8H), 3.35–3.39 (m, 8H), 3.47 (s, 4H), 4.43 (s, 8H),
4.84–4.96 (m, 4H), 6.18 (s, 1H), 6.82–6.99 (m, 8H),
7.19 (d, 1H, J = 8.9 Hz), 7.35 (d, 1H, J = 8.9 Hz), 7.55–
7.56 (m, 4H). 13C NMR (CDCl3, 62.9 MHz) δ = 18.8,
35.0, 37.4, 51.4, 57.1, 60.7, 66.7, 80.4, 81.4, 110.2,
112.2, 112.3, 112.4, 119.9, 122.1, 146.0, 152.5, 153.5,
160.1, 167.2. Anal. Calcd. for C46H50N6O12 (878.929):
C, 62.86; H, 5.73. Found: C, 62.72; H, 5.61.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of [Zn(II)BHPPDAH] as New Heterogeneous Catalyst without Immobilization, and Applying Mannich Reaction 383
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Heteroatom Chemistry DOI 10.1002/hc