Tandem reaction of Morita-Baylis-Hillman alcohols derived from acrylic nitrile with 2-aminobenzimidazole in ionic liquid [BMIM]Cl/H2O

Article abstract of DOI:10.1139/v11-095

The tandem reaction of Morita-Baylis-Hillman (MBH) alcohols 1a-1l derived from acrylic nitrile with 2-aminobenzimidazole (2) in ionic iquid (IL) [BMIM]Cl/H₂O without additional catalyst was developed for the efficient synthesis of benzimidazol[

Full text of DOI:10.1139/v11-095

85
Tandem reaction of Morita–Baylis–Hillman alcohols
derived from acrylic nitrile with 2-
aminobenzimidazole in ionic liquid [BMIM]Cl/H2O
Yan Wang, Li Liu, Dong Wang, and Yong-Jun Chen
Abstract: The tandem reaction of Morita–Baylis–Hillman (MBH) alcohols 1a–1l derived from acrylic nitrile with 2-amino-
benzimidazole (2) in ionic iquid (IL) [BMIM]Cl/H2O without additional catalyst was developed for the efficient synthesis of
benzimidazol[1,2-a]pyrimidin-7(8H)-imine compounds. The tandem reaction included aza-Michael addition and intramolecu-
lar addition of an amino group to the cyano group in one pot. The combination of ionic liquid and water was found to be
the best reaction medium, which played a role for accelerating the tandem reaction.
Key words: Morita–Baylis–Hillman, ionic liquids, catalyst-free, aza-Michael addition.
Résumé : Comme méthode de synthèse efficace des dérivés de la benzimidazo[1,2-a]pyrimidine-7(8H)-imine, on a mis au
point une réaction en tandem de Morita–Baylis–Hillman (MBH) d’alcools 1a–1l dérivés de l’acrylonitrile avec du 2-amino-
benzimidazole (2) dans un liquide ionique (LI) formé de chlorure de 1-butyl-3-méthylimidazolium (BMIM) et d’eau, sans
addition de catalyseur. La réaction en tandem comporte une addition d’aza-Michael et une addition intramoléculaire du
groupe amino sur le groupe cyano dans une réaction monotope. On a trouvé que la combinaison du liquide ionique et de
l’eau est le meilleur milieu réactionnel qui joue un rôle d’accélérateur dans la réaction en tandem.
Mots‐clés : Morita–Baylis–Hillman, liquides ioniques, sans catalyseur, addition d’aza-Michael.
[Traduit par la Rédaction]
tion of MBH alcohols derived from acrylic nitrile with 2-
aminobenzoimidazole should be very interesting for the de-
velopment of an efficient protocol accessible to the novel
fused aza-heterocyclic compounds.
On the other hand, in recent years, ionic liquids (ILs) have
attracted considerable attention as an alternative solvent in or-
ganic reactions because of their tunable physical properties,
such as their almost nonvolatile nature, high thermal stability,
strong solvating ability to a great number of organics, inor-
ganics and polymers, reusability, and recyclability. Several
ILs have been successfully used as solvents and promoters in
a lot of chemical transformations.6
Introduction
The Morita–Baylis–Hillman (MBH) reactions have proved
to be one of the most successful methods for C–C bond-
forming reactions. Since three functionalized groups, the hy-
droxyl group, the double bond, and the carbonyl (cyano)
group, lie closely in one molecule, the MBH adducts are suit-
able precursors for the synthesis of many heterocycles and
biologically active molecules.1 Particularly, the Michael addi-
tion of the amine to the double bond of an MBH adduct’s
molecule and the subsequent functionalization have been em-
ployed in the synthesis of many aza-heterocycles.2
Imidazo[1,2-a]pyrimidines are very important intermediates
and are widely used in the pharmaceutical chemistry, such as
for the synthesis of the antianxiety drug divaplon (A) (Fig. 1).3
Among them, several 7-amino-imidazo[1,2-a]pyrimidine de-
rivatives also exhibited interesting biological activities includ-
ing as GABAA receptors (B) (Fig. 1).4 Recently, we reported
the efficient synthesis of benzimidazo[1,2-a]pyrimidinone via
a catalyst-free tandem reaction of MBH adducts bearing an
ester unit with 2-aminobenzimidazole.5 In general, the reac-
tion containing the nitrile compound as a substrate is one of
the most efficient approaches for introducing an amino
group into a molecule. We envisioned that the tandem reac-
Herein, we will report a tandem reaction of MBH alcohols
derived from acrylic nitrile and aldehydes with 2-aminoben-
zimidazole7 in ILs with a small amount of water without any
additional catalyst to produce novel fused aza-heterocyclic
compounds.
Results and discussion
Initially, under the condition that is similar to the reaction
of MBH alcohol derived from acrylic ester with 2-aminobenz-
imidazole (2),5 the reaction of MBH alcohol 1h derived
from benzaldehyde and acrylic nitrile with 2 was carried
Received 16 March 2011. Accepted 30 May 2011. Published at www.nrcresearchpress.com/cjc on 1 November 2011.
Y. Wang, L. Liu, D. Wang, and Y.-J. Chen. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of
Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China. Yan Wang
Graduate School of Chinese Academy of Sciences, Beijing 100049, P. R. China.
Corresponding author: Li Liu (e-mail: lliu@iccas.ac.cn).
This article is part of a Special Issue dedicated to Professor Tak-Hang Chan.
Can. J. Chem. 90: 85–91 (2012)
doi:10.1139/V11-095
Published by NRC Research Press

86
Can. J. Chem. Vol. 90, 2012
Fig. 1. Divaplon (A) and GABAA receptors (B).
to be the most efficient reaction medium for this tandem re-
action.
MeO
N
NR'R''
N
N
N
With optimized conditions in hand, we examined the scope
of the MBH alcohols derived from acrylic nitrile9 with 2 in
IL [BMIM]Cl/H2O (11:1) at 100 °C in the absence of any
additional catalyst (Scheme 1). The results are summarized
in Table 3. As shown in Table 3, the reactions of various
MBH alcohols (1a–1l) derived from acrylic nitrile proceeded
smoothly in a period of 6 h to form the corresponding prod-
ucts 3a–3l in good yields. The electronic properties of the
substituents of MBH alcohols had no effect on the reaction.
The MBH alcohol 1k bearing the steric group also generated
the product 3k in 89% yield (Table 3, entries 11). Although
much a longer reaction time (48 h) was needed, alkyl-substituted
MBH alcohol 1l could also give the expected product 3l in
good yield (75%) (Table 3, entry 12).
In terms of a plausible mechanism for the nucleophilic re-
action with imidazole,7b the route of the reaction of MBH alco-
hols 1 derived from acrylic nitrile with 2-aminobenzimidazole
(2) was proposed as shown in Scheme 2. In the first step,
the nitrogen atom at the 3 position of 2-aminobenzimidazole
attacked at the a,b-unsaturated carbon atom of the MBH al-
cohol in a Michael-addition manner to generate an inter-
mediate I (path A). In this step, ILs, especially [BMIM]Cl
containing a small amount of water, played the roles of
both reaction medium and accelerator.8 It was noteworthy
that since the MBH alcohols 1 derived from acrylic nitrile
were unstable to water and could be decomposed through
retro-MBH reaction at high temperature, the water percent-
age in the IL was confined to a small range: H2O:IL =
1:11 ∼ <1:4. In the second step (path B), the intermediate
I underwent an intramolecular addition reaction of an amino
group to the cyano group, giving cyclization product 3. In
general, for the addition reaction of an amino group to the
cyano group a suitable catalyst or a relatively higher reac-
tion temperature were required. Thus, in a catalyst-free sys-
tem a high reaction temperature (100 °C) had to be
employed unavoidably.
N
N
Et
R
Ar
Me
A, Divaplon
B
out in dioxane at 80 °C (Table 1, entry 1). However, the
yield of the product 3h was very low. Although various or-
ganic solvents were used, the yields of 3h were unsatisfac-
tory either (Table 1, entries 2–6), even in the presence of
K2CO3 as a catalyst (Table 1, entry 7). But the reaction of
1h with 2 could proceed smoothly in water (Table 1, entry
8). Unfortunately, when the aqueous condition was em-
ployed to other substrates, such as 1a, the reaction with 2
became sluggish and the products were complicated (Ta-
ble 2, entries 1 and 2). This is probably attributed to the
poor solubility and stability of the MBH alcohol 1a in
water at high temperature. To improve the solubility of the
MBH alcohols and 2, the ionic liquids were selected to be
reaction media. If ionic liquid [BMIM]Cl was used as a
medium for the reaction of 1a with 2 at 100 °C, a homoge-
neous solution was formed and the product, 6-(4-chlorophen-
ylhydroxylmethyl)-5,6-dihydro-benzimidazo-[1,2-a]pyrimidin-
7(8H)-imine (3a), was obtained in 53% yield (Table 2,
entry 3). To our delight, the addition of a small amount of
water to the medium ([BMIM]Cl/H2O = 11:1) led the yield
of 3a to increase (Table 2, entries 4 and 5). It was probably
that the small amount of water could promote this reaction.8
The tandem reaction did not need any additional catalyst for
the high yield of the final product 3a. However, when the
water percentage in the reaction medium was increased to
4:1 ([BMIM]Cl/H2O), the yield of 3a was decreased sharply
to 6%. It is proposed that the substrate 1a decomposed
under the conditions with such a large amount of water
(Table 2, entry 6).
Based on these results, various ILs (Fig. 2) were employed
in the reaction of 1a with 2 as reaction media containing a
small amount of water (IL/water = 11:1). As shown in Ta-
ble 2 for the same cation ([BMIM]+), the anions of the ILs
used strongly influnced the yields of the product 3a (Table 2,
entry 5 vs entries 7–9). Moreover, with the same anion
Conclusion
In conclusion, we have developed an efficient method for
the synthesis of fused aza-heterocyclic compounds, benzimid-
azo[1,2-a]pyrimi-din-7(8H)-imine derivatives in good to
excellent yields via a tandem reaction of BMH alcohols
(1a–1l) with 2-aminobenzoimidazole in IL/H2O. The devel-
oped protocol was simple and catalyst free. The reaction
underwent the Michael addition reaction, followed by intra-
molecular cyclization in a one-pot process. The produced
fused heterocyclic compounds provided an opportunity to
enhance the diversity of benzimidazo[1,2-a]pyrimidine com-
pounds by further derivation.
–
(BF4 ) the molecular structure of the ammonium ion also has
a strong effect on the reaction. It was found that [EMIM]+
bearing an N-ethyl group and [OMIM]+ bearing an N-octyl
group provided poor yields of 3a (Table 2, entries 10 and
11, respectively), but for [BMIM]+ bearing an N-butyl group
a 74% yield of 3a was obtained (Table 2, entry 9). In com-
parison with [BMIM]+, the change of the N′-substituent
from a methyl to a vinyl group ([BEIM]+) and introduction
of a second methyl group ([BDMIM]+) provided a compli-
cated product mixture and very poor yield of 3a (Table 2, en-
tries 12 and 13) despite having the same core structure of
imidazole. The employment of the pyridine unit ([NBPD]+)
as a cation part did not improve the yield of 3a at all (Ta-
ble 2, entry 14). Interestingly, the use of organic solvents
with a small amount of water (Sol/H2O = 11:1) also afforded
a complicated mixture of the products (Table 2, entries 15
and 16). In summary, the IL [BMIM]Cl/water was determined
Experimental
Typical procedure for the reaction of MBH alcohol (1)
with 2-aminobenzimidazole (2)
To a solution of MBH alcohol 1a (97 mg, 0.5 mmol) and
2 (100 mg, 0.75 mmol) in 0.5 mL of IL [BMIM]Cl was
added water (40 µL, 2.5 mmol). The resulting mixture was
heated at 100 °C until completion as indicated by TLC.
Then the reaction mixture was extracted by ethyl acetate and
Published by NRC Research Press

Wang et al.
87
Table 1. The reaction of Morita–Baylis–Hillman (MBH) alcohol 1h with 2.
OH NH
NH
OH
CN
N
solvent
NH2
N
H
N
N
3h
2
1h
Entry
Solvent
Dioxane
MeOH
THF
T (°C)
80
Reflux
Reflux
Reflux
80
80
50
80
Time (h)
14
14
14
14
14
14
24
14
Yield (%)a
45
10
18
44
1
2
3
4
5
6
7b
8
DCM
CH3CN
Toluene
Toluene
H2O
18
20
30c
100
Note: Reaction conditions: 1h (0.5 mmol), 2 (0.75 mmol), and solvent (0.5 mL).
1
aDetermined by H NMR.
bWith K2CO3 (10 mol%).
cIsolated yield.
Table 2. The reaction of Morita–Baylis–Hillman (MBH) alcohol 1a with 2.
OH NH
NH
OH
100 oC
Cl
CN
N
NH2
N
H
N
Cl
N
3a
2
1a
Entry
1
Reaction medium
H2O
H2O
Time (h)
Yield (%)a
b
6
6
1
1
4
4
3
3
3
4
4
4
4
4
6
5
—
—
53
66
85
6
b
2c
3
[BMIM]Cl
[BMIM]Cl
[BMIM]Cl
[BMIM]Cl
[BMIM]SbF6
[BMIM]PF6
[BMIM]BF4
[EMIM]BF4
[OMIM]BF4
[BEIM]BF4
[BDMIM]BF4
[NBPD]BF4
MeOH
4d
5d
6e
7d
—
46
74
50
—
—
—
—
—
—
b
8d
9d
10d
11d
b
b
b
b
b
b
d
12
13d
d
14
15
16
d
d
THF
Note: Reaction conditions: 1a (0.5 mmol), 2 (0.75 mmol), and solvent (0.5 mL), at 100 °C or reflux.
aIsolated yield.
bcomplicated products with poor yield of 3a.
cAt 80 °C.
dH2O (2.5 mmol) was added.
e[BMIM]Cl (0.4 mL) : H2O (0.1 mL) = 4:1.
water. The organic phase was dried by Na2SO4 and purified
by column chromatography over silica gel (eluent: DCM–
MeOH = 100:2) to afford a light yellow solid 3a (139 mg,
85%).
3.53–3.67 (1H, m, –CH), 4.21–4.54 (2H, m, –CH2), 4.89–
4.98 (1H, m, –CH), 6.47–6.56 (3H, m, –NH, –NH, –OH),
6.88–6.98 (2Harom, m), 7.03–7.27 (2Harom, m), 7.46–7.49
(4Harom, m). dC (300 MHz. DMSO-d6, TMS): 40.4, 41.2,
68.4, 70.3, 107.7, 107.8, 114.9, 118.0, 118.2, 118.3, 118.7,
120.7, 127.6, 128.2, 128.3, 128.6, 132.2, 132.7, 133.9,
3a, light yellow solid, mp 161–163 °C. nmax (KBr, cm–1):
3471, 3371, 3055, 1547. dH (300 MHz, DMSO-d6, TMS):
Published by NRC Research Press

88
Can. J. Chem. Vol. 90, 2012
Fig. 2. Ionic liquids employed in the reaction of Morita–Baylis–
Hillman (MBH) alcohols with 2.
6.86–6.99 (2.3Harom, m), 7.12–7.16 (1Harom, m), 7.22–7.34
(1.7Harom
,
m), 7.45–7.54 (1.7Harom
,
m), 7.65–7.74
(1.3Harom, m). dC (300 MHz, DMSO-d6, TMS): 16.9, 37.2,
37.9, 38.3, 40.5, 67.3, 69.8, 107.6, 107.8, 114.8, 114.9,
117.3, 118.3, 118.5, 118.6, 118.7, 120.3, 120.9, 121.0,
122.2, 127.8, 128.1, 128.3, 128.8, 130.0, 130.3, 132.3,
132.6, 133.5, 133.7, 134.3, 139.7, 140.1, 142.1, 142.3,
154.4, 154.8. HRMS (EI) m/z calcd for C17H16BrN4O (M +
1)+: 371.0497; found: 371.0502
+
+
+
N
N
N
N
N
N
BMIM
EMIM
OMIM
+
+
+
N
N
N
N
N
3g, light yellow solid, mp 129–131 °C. nmax (KBr, cm–1):
3444, 3352, 3150, 1547. dH (300 MHz, DMSO-d6, TMS):
3.52–3.66 (1H, m, –CH), 4.27–4.54 (2H, m, –CH2), 4.88–
4.98 (1H, m, –CH), 6.42–6.56 (3H, m, –NH, –NH, –OH),
6.91–7.27 (6Harom, m), 7.48–7.55 (2Harom, m). dC (300 MHz,
DMSO-d6, TMS): 40.6, 41.2, 68.5, 70.3, 107.7, 107.8, 114.8,
118.0, 115.1, 115.2, 118.1, 118.2, 118.3, 118.8, 120.7, 127.7,
128.2, 127.8, 128.7, 128.8, 133.9, 134.3, 137.3, 138.1, 138.2,
142.6, 142.7, 154.7, 154.9, 160.0, 160.3. HRMS (EI) m/z
calcd for C17H16FN4O (M + 1)+: 311.1299; found: 311.1302.
3h, light yellow solid, mp 171–173 °C. nmax (KBr, cm–1):
3462, 3374, 3062, 1548. dH (300 MHz, DMSO-d6, TMS):
3.51–3.69 (1H, m, –CH), 4.22–4.55 (2H, m, –CH2), 4.85–
4.95 (1H, m, –CH), 6.38–6.61 (3H, m, –NH, –NH, –OH),
6.86–7.01 (2.5Harom, m), 7.13–7.16 (1Harom, m), 7.24–7.45
(5.5Harom, m). dC (300 MHz, DMSO-d6, TMS): 41.1, 41.8,
69.4, 71.5, 108.3, 115.2, 118.7, 119.4, 121.3, 126.2, 127.2,
128.2, 128.7, 134.4, 134.7, 141.6, 142.5, 142.9, 155.2.
HRMS (EI) m/z calcd for C17H17N4O (M + 1)+: 293.1393;
found: 293.1397.
BEIM
BDMIM
NBPD
134.2, 140.0, 141.0, 142.6, 142.7, 154.7, 154.8. HRMS (EI)
m/z calcd for C17H16ClN4O (M + 1)+: 327.1007; found:
327.1004.
3b, light yellow solid, mp 138–140 °C. nmax (KBr, cm–1):
3444, 3353, 3058, 1547. dH (300 MHz, DMSO-d6, TMS):
3.57–3.59 (1H, m, –CH), 4.26–4.51 (2H, m, –CH2), 4.91–
5.00 (1H, m, –CH), 6.46–6.56 (3H, m, –NH, –NH, –OH),
6.88–6.98 (2Harom, m), 7.04–7.59 (6Harom, m). dC (300 MHz,
DMSO-d6, TMS): 40.5, 41.3, 68.4, 70.4, 107.8, 107.9, 114.8,
118.0, 118.4, 118.4, 118.7, 120.8, 124.4, 125.5, 125.7, 126.6,
127.6, 128.1, 130.1, 133.0, 133.1, 133.9, 134.2, 142.4, 142.6,
143.6, 144.5, 154.8. HRMS (EI) m/z calcd for C17H16ClN4O
(M + 1)+: 327.1007; found: 327.1007.
3c, light yellow solid, mp 108–110 °C. nmax (KBr, cm–1):
3444, 3353, 3060, 1546. dH (300 MHz, DMSO-d6, TMS):
3.53–3.65 (1H, m, –CH), 4.47–4.55 (2H, m, –CH2), 4.89–
5.39 (1H, m, –CH), 6.44–6.57 (3H, m, –NH, –NH, –OH),
6.87–7.02 (2.5Harom, m), 7.13–7.17 (1Harom, m), 7.28–7.48
(3.5Harom, m), 7.73–7.70 (1Harom, m). dC (300 MHz, DMSO-
d6, TMS): 38.0, 38.3, 40.6, 65.2, 67.4, 107.6, 107.8, 114.9,
117.5, 118.3, 118.6, 118.7, 121.0, 127.3, 127.6, 128.0,
128.6, 129.1, 129.3, 129.6, 129.9, 130.1, 131.7, 133.7,
134.2, 138.2, 138.8, 142.2, 142.3, 154.7, 154.8. HRMS (EI)
m/z calcd for C17H16ClN4O (M + 1)+: 327.1007; found:
327.1003.
3i, light yellow solid, mp 150–152 °C. nmax (KBr, cm–1):
3430, 3354, 3221, 1546. dH (300 MHz, DMSO-d6, TMS):
3.53–3.67 (1H, m, –CH), 3.76–3.78 (3H, m, –OCH3), 4.22–
4.54 (2H, m, –CH2), 4.83–4.94 (1H, m, –CH), 6.37–6.57
(3H, m, –NH, –NH, –OH), 6.89–7.34 (8Harom, m). dC
(300 MHz, DMSO-d6, TMS): 39.3, 40.5, 41.3, 55.0, 55.0,
68.9, 70.9, 107.7, 107.8, 111.6, 112.2, 112.9, 113.7, 114.9,
117.9, 118.2, 118.9, 120.7, 129.3, 129.4, 134.0, 134.3,
131.5, 142.6, 142.7, 143.7, 154.7, 154.9, 159.2, 159.2
HRMS (EI) m/z calcd for C18H19N4O2 (M + 1)+: 323.1498;
found: 323.1503.
3d, light yellow solid, mp 149–151 °C. nmax (KBr, cm–1):
3477, 3371, 3054, 1546. dH (300 MHz, DMSO-d6, TMS):
3.50–3.70 (1H, m, –CH), 4.20–4.53 (2H, m, –CH2), 4.86–
4.96 (1H, m, –CH), 6.45–6.54 (3H, m, –NH, –NH, –OH),
6.85–6.99 (2Harom, m), 7.03–7.27 (2Harom, m), 7.39–7.63
(4Harom, m). dC (300 MHz, DMSO-d6, TMS) 40.4, 41.2,
68.5, 70.3, 107.7, 107.9, 114.8, 114.8, 118.0, 118.2, 118.3,
118.7, 120.8, 121.3, 128.0, 129.0, 131.1, 131.2, 133.9,
134.2, 140.5, 141.4, 142.5, 142.7, 154.7, 154.8. HRMS (EI)
m/z calcd for C17H16BrN4O (M + 1)+: 371.0497; found:
371.0502.
3j, light yellow solid, mp 173–175 °C. nmax (KBr, cm–1):
3444, 3354, 3053, 1546. dH (300 MHz, DMSO-d6, TMS):
3.55–3.70 (3H, m, –CH3), 3,81 (1H, s, –CH), 4.10–4.57
(2H, m, –CH2), 4.82–5.30 (1H, m, –CH), 6.09–6.55 (3H, m,
–NH, –NH, –OH), 6.81–7.27 (7Harom, m), 7.53–7.55 (1Harom, m).
dC (300 MHz, DMSO-d6, TMS): 14.0, 20.7, 37.8, 37.9,
40.8, 54.9, 55.4, 59.7, 63.4, 65.2, 107.4, 107.8, 110.2,
110.9, 114.8, 114.9, 118.2, 118.2, 118.3, 119.1, 120.2,
120.4, 120.7, 120.8, 126.2, 127.4, 128.7, 129.3, 129.7,
133.8, 134.3, 142.6, 142.7, 154.8, 154.9, 155.9. HRMS
(EI) m/z calcd for C18H19N4O (M + 1)+: 307.1549; found:
307.1553.
3e, light yellow solid, mp 152–154 °C. nmax (KBr, cm–1):
3452, 3368, 3065, 1552. dH (300 MHz, DMSO-d6, TMS):
3.57–3.69 (1H, m, –CH), 4.25–4.51 (2H, m, –CH2), 4.89–
4.96 (1H, m, –CH), 6.45–6.54 (3H, m, –NH, –NH, –OH),
6.88–6.99 (2Harom, m), 7.02–7.73 (6Harom, m). dC (300 MHz,
DMSO-d6, TMS): 41.0, 41.9, 68.9, 70.9, 108.3, 108.4, 115.4,
118.5, 118.9, 119.3, 121.3, 122.1, 122.3, 125.3, 126.4, 129.1,
130.0, 130.9, 131.0, 131.5, 134.4, 134.8, 143.0, 143.1, 144.3,
145.3, 155.3, 155.4. HRMS (EI) m/z calcd for C17H16ClN4O
(M + 1)+: 371.0497; found: 371.0502
3k, light yellow solid, mp 168–170 °C. nmax (KBr, cm–1):
3444, 3353, 3221, 1546. dH (300 MHz, DMSO-d6, TMS):
1.89 (1.5H, m, –CH3), 2.30–2.33 (4.5H, m, –CH3), 3.37–
3.64 (1H, m, –CH), 4.34–4.60 (2H, m, –CH2), 4.79–5.16
(1H, m, –CH), 6.17–6.59 (3H, m, –NH, –NH, –OH), 6.88–
7.30 (6Harom, m), 7.41–7.47 (1Harom, m). dC (300 MHz,
DMSO-d6, TMS): 17.4, 18.5, 20.7, 20.9, 38.5, 40.5, 40.9,
65.0, 67.5, 107.7, 107.8, 114.9, 115.0, 118.0, 118.3, 118.5,
118.7, 120.8, 120.8, 126.4, 127.0, 128.1, 128.5, 130.1,
3f, light yellow solid, mp 171–173 °C. nmax (KBr, cm–1):
3444, 3352, 3057, 1546. dH (300 MHz, DMSO-d6, TMS)
3.48–3.71 (1H, m, –CH), 4.27–4.60 (2H, m, –CH2), 4.81–
5.32 (1H, m, –CH), 6.49–6.60 (3H, m, –NH, –NH, –OH),
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Wang et al.
89
Scheme 1 The reactions of Morita–Baylis–Hillman (MBH) alcohols with 2.
OH NH
NH
OH
N
R
CN
NH2
+
R
N
H
[BMIM]Cl/H2O (11:1), 100 °C
N
3a-3l
N
1a-1l
R: aryl, alkyl
2
Table 3. The reaction of Morita–Baylis–Hillman (MBH) alcohols 1a–1l with 2 in IL/H2O without catalyst (IL, ionic liquid).
Entry
1
MBH alcohol
1a
Time (h)
4
Product
3a
Yield (%)
85
OH NH
NH
OH
CN
Cl
N
Cl
N
2
1.5
88
1b
3b
OH NH
OH
Cl
Cl
CN
NH
N
N
3
83
3
Cl
OH NH
NH
1c
Cl
OH
3c
CN
N
N
4
75
4
OH NH
NH
1d
OH
3d
CN
Br
N
Br
N
1.5
91
5
OH NH
1e
OH
3e
Br
Br
CN
NH
N
N
2
80
6
Br
OH NH
NH
1f
Br
OH
3f
CN
N
N
7
4
OH NH
NH
85
1g
OH
3g
CN
N
F
F
N
130.2, 131.9, 134.0, 134.4, 134.6, 135.0, 139.3, 139.6, 142.6,
142.8, 154.8, 155.0. HRMS (EI) m/z calcd for C19H21N4O
(M + 1)+: 321.1706; found: 321.1710.
0.86–0.98 (3H, m, –CH3), 1.46–1.76 (2H, m, –CH2), 3.21
(1H, m, –CH), 3.51–3.59 (1H, m, –CH), 4.17–4.44 (2H, m,
–CH2), 5.48–5.60 (1H, m, –CH), 6.51 (3H, s, –NH, –NH, –OH),
3l, light yellow solid, mp 110–112 °C. nmax (KBr, cm–1):
3430, 3352, 2966, 1547. dH (300 MHz, DMSO-d6, TMS):
6.88–6.99 (2Harom
,
m), 7.41–7.24 (2Harom
,
m). dC
(300 MHz, DMSO-d6, TMS): 10.0, 10.0, 16.8, 28.2, 37.7,
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90
Can. J. Chem. Vol. 90, 2012
Table 3. (concluded).
Entry
8
MBH alcohol
Time (h)
5
Product
3h
Yield (%)
83
1h
OH NH
NH
OH
CN
N
N
4
9
1i
OH NH
NH
3i
88
OH
MeO
MeO
CN
N
N
10
3
1j
OH NH
OH
3j
76
CN
NH
Me
N
Me
N
6
11
1k
Me OH NH
NH
3k
89
Me OH
CN
N
N
Me
Me
48
12
1l
OH NH
NH
3l
75
OH
CN
N
N
Scheme 2. Plausible mechanism.
OH
OH NH
NH
N
NH2
NH
R
R
[BMIM]Cl/H2O (11:1), 100oC
N
1
N
N
3
2
A
path
-H, +H
N
OH
OH
N
N
N
OH
NH2
NH2
N
NH2
N
R
R
R
path B
-H
NH
N
N
+H
I
II
III
Acknowledgement
38.2, 39.8, 40.8, 68.7, 69.5, 107.9, 114.8, 114.9, 118.3,
118.3, 118.8, 119.3, 120.7, 120.8, 134.0, 134.2, 142.5,
142.7, 154.8, 154.8. HRMS (EI) m/z calcd for C13H16N4O
(M + 1)+: 245.1395; found: 245.1397.
We are grateful to the National Natural Foundation of China,
Ministry of Science and Technology (No. 2009ZX09501-006),
and the Chinese Academy of Sciences for financial support.
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Wang et al.
91
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Suarez, P. A. Z. Chem. Rev. 2002, 102 (10), 3667. doi:10.1021/
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P.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Chem. Rev.
2008, 108 (6), 2015. doi:10.1021/cr078399y.
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