The unprecedented C-alkylation and tandem C-/O-alkylation of phenanthrolinium salts with cyclic 1,3-dicarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2011.02.063

N-p-Nitrobenzyl- or N-phenacylphenanthrolinium bromides reacted with a series of cyclic 1,3-dicarbonyl compounds in acetonitrile in the presence of triethylamine as base catalyst to give the unprecedented C-alkylated products and tandem alkylated/intramol

Full text of DOI:10.1016/j.tet.2011.02.063

Tetrahedron 67 (2011) 2863e2869
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The unprecedented C-alkylation and tandem C-/O-alkylation of phenanthrolinium
salts with cyclic 1,3-dicarbonyl compounds
*
Hui Li, Chao-Guo Yan
College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
N-p-Nitrobenzyl- or N-phenacylphenanthrolinium bromides reacted with a series of cyclic 1,3-dicarbonyl
compounds in acetonitrile in the presence of triethylamine as base catalyst to give the unprecedented
C-alkylated products and tandem alkylated/intramolecular O-alkylated oxazabicyclic compounds ac-
cording to the structure of cyclic 1,3-dicarbonyl compounds.
Received 19 December 2010
Received in revised form 22 January 2011
Accepted 22 February 2011
Available online 2 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Phenanthroline
Pyridinium salt
Meldrum acid
Dimedone
Tandem reaction
1. Introduction
2. Results and discussions
The heterocyclic ammonium salts, especially those bearing an
active methylene group have versatile reactivity and were used in
a great variety of synthetic reactions for constructing polycyclic
systems.1,2 The most popular used heterocyclic ammonium salt is
At first we investigated the three-component reaction of N-p-
nitrobenzylphenanthrolinium bromide (1a), aromatic benzalde-
hyde, and dimedone according to our previously established
condition for pyridinium and isoquinolinium salts.13 The mixture of
the three components in acetonitrile with triethylamine as base
catalyst was carried out at room temperature for several hours. After
workup we were surprised to find that the separated product is 3a,
and its structure clearly showed that aromatic aldehyde did not take
part in the reaction. Thus no aromatic aldehyde was utilized in the
further reactions. The reaction of N-p-nitrobenzylphenanthrolinium
bromide (1a) with dimedone (2a) in acetonitrile with triethylamine
as base catalyst proceeded smoothly to give the product (3a) in 66%
yields. Then other cyclic 1,3-dicarbonyl compounds were also tested
in the reactions (Equation 1). We are pleased to find that 1,3-cyclo-
hexanedione, coumarin also formed the similar oxazabicyclic de-
rivatives 3b (47%) and 3c (53%) in moderate yields (Scheme 1). On
the other hand the reaction of N-p-nitrobenzylphenanthrolinium
bromide (1a) with Meldrum acid, N,N-dimethylbarbituric acid, thi-
obarbituric acid, 1,3-cyclopentanedione, and 1,3-thiazolidinedione
in acetonitrile in the presence of triethylamine gave completely C-4
alkylated products 4aee in 43e87% yields. Thus two kinds of
products can be obtained from the base catalyzed reaction of cyclic
1,3-dicarbonyl compounds with phenanthrolinium bromide
according to the structures of the cyclic 1,3-dicarbonyl compounds.
pyridinium salt. Pyridinium salts with
a-halogenocarbonyl com-
pounds are easily deprotonated to give pyridinium ylide, which are
prone to be high potential synthons3 and undergo many types of
reactions, such as Michael addition,4,5 1,3-dipolar cycloaddition,6e8
substitution, and others.2c,9,10 Then the quinolinium and iso-
quinolinium salts are also attracted much attention because they
often showed different reaction modes to the corresponding pyr-
idinium salts.11,12 In the past few years we have successfully de-
veloped several tandem reaction based on the in situ formed
reactive pyridinium salts and isoquinolinium salts.13 In continua-
tion of our efforts to investigate new tandem reactions we want to
develop this kind of reactions to other nitrogen-containing het-
erocyclic systems. Here we wish to report the very interesting re-
actions of phenanthrolinium bromides with cyclic 1,3-dicarbonyl
compounds and the efficient synthesis of pyran-bridged phenan-
throline derivatives.
* Corresponding author. E-mail address: cgyan@yzu.edu.cn (C.-G. Yan).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.063

2864
H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
O
E
N
N
O
O2N
3a-3c
O
N
N
E
Et3N
+
E
Br
CH3CN, r.t.
O
O
O
NO2
N
N
1a
2a-2h
NO2
4a-4e
Equation 1. Reactions of N-p-nitrobenzylphenanthrolinium bromide (1a) with cyclic
1,3-diketones.
The structures of the prepared products 3aec and 4aee
(Scheme 1) were fully characterized by elemental analysis,1H and 13
C
NMR, MS, IR spectra, and were further confirmed by single-crystal X-
ray diffraction studies performed for three representatives com-
pounds 3a (Fig. 1), 3c, and 4a (Fig. 2). From Fig. 1 we clearly saw that
the C-2 and C-4 position of phenanthroline ring were both connected
withtheC-2andcarbonyloxygenatomofdimedone, whichobviously
formed from the tandem C-4 C-alkylated and intramolecular C-2 O-
alkylated of dimedone. Form Fig. 2 we could see that phenanthroline
ring was connected with Meldrum acid by C]C double bond. As one
of the typical heterocyclic compounds phenanthroline and its
derivatives perform interesting chemical activities. 1,10-Phenan-
throline and its derivatives have long been known as commonly used
ligands in coordination chemistry and catalytic organic synthesis.
Sometimes the uses of functionalized phenanthrolines have been
Fig. 1. The molecular structure of compound 3a.
limited, which is in part due to the lack of efficient synthetic
methods.14 The efficiency and ease of handling of this reaction should
render this reaction applicable to the synthesis of functionalized
phenanthrolines. Tothe bestof ourknowledge, there are no reportsof
this kind of oxazabicyclic system based on phenanthroline ring in the
literature. A few examples about the oxazabicyclic compounds based
on quinoline and isoquinoline have been reported in recently
years.15e18 This year Moghaddam described the addition reactions of
1,3-dicarbonyl compounds to quinolinium salts for the convenient
synthesis of the oxazabicyclic systems.19 Here we have successfully
O
O
N
O
O
O
O
O
O
N
N
N
O
N
N
O
N
N
O
NO2
NO2
NO2
NO2
3a (66%)
3b (47%)
3c (53%)
4a (87%)
S
O
N
O
H
HN
O
N
O
N
O
O
O
NH
O
S
O
N
N
N
N
N
N
N
N
NO2
NO2
NO2
NO2
4b (61%)
4c (49%)
4d (86%)
4e (43%)
Scheme 1. The prepared phenanthroline derivatives 3aec and 4aee.

H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
2865
Fig. 2. The molecular structure of compound 4a.
provided an efficient synthetic method for the functionalized oxa-
zabicyclic phenanthroline derivatives.
single-crystal structures of the oxazabicyclic compound 5b (Fig. 3)
and the C-4 alkylated phenanthroline 6b (Fig. 4) were determined by
X-ray diffraction. These results showed that the reaction of phenan-
throlinium salts with cyclic 1,3-dicarbonyl compounds is atom effi-
cient and applicable to a wide variety of substrates.
To further demonstrate the superiority of our methodology and to
extend the utility of this reaction, the reactions of N-phenacylphe-
nanthrolinium bromides 1b with different kinds of cyclic 1,3-dicar-
bonyl compounds were also explored (Equation 2). Under similar
reaction conditions the N-phenacylphenanthrolinium bromides 1b
reacted with dimedone, 1,3-cyclohexanedione, and coumarin gave
the oxazabicyclic compounds 5aec in good yields. The expected
C-alkylation products 6aeb were also obtained from the reaction of
1b with Meldrum acid and 1,3-cyclopentanedione (Scheme 2). The
To explain the formation mechanism of the two kinds of prod-
ucts in the reaction, we proposed a plausible reaction mechanism,
which is shown in Scheme 3. In phenanthrolinium cation 1 the
electrophilic effect of the positive nitrogen makes 2- and 4-position
of the aza-cycle relatively electropositive. In other words the pos-
itive charge is spread to the C-2 and C-4 carbon atoms (A). So C-2
and C-4 carbon atoms become more susceptible to attack by nu-
cleophiles. The cyclic 1,3-dicarbonyl compound is deprotonated by
triethylamine to yield the carbanion. The latter in turn attacks the
carbon atom of 4-position of phenanthrolinium cation (A) to give
the intermediate (B). Due to the strong electron-withdrawing effect
of two carbonyl groups intermediate (B) was deprotonated further
to give a new carbanion (C) in the presence of triethylamine. Then
intermediate (C) reacts further to two different paths that will yield
two different products. On the first reaction path, the carbanium (C)
transferred to resonance-stabilized enolate ion (D) through the
ketoeenol tautomerization, which in turn attack the relative pos-
itive C-2 to give the final oxazabicyclic compound 3 with additional
protonation step. On the second path, the carbanium (C) was
dehydrogenated in air to form a C]C bond between the C-4 of
phenanthroline ring and C-2 of Meldrum acid, which resulted in
the compound 4 as the final product. We believed that in this
proposed reaction mechanism the formation and stability of eno-
late ion of the cyclic 1,3-dicarbonyl compounds controls the for-
mation of two different products. The stronger acidities of Meldrum
acid and related dicarbonyl compounds would be due to its strong
O
E
N
N
O
O
O
5a-5c
N
N
Et3N
Br
O
+
E
E
CH3CN, r.t.
O
O
O
1b
2a-2e
N
N
O
6a-6b
Equation 2. Reactions of N-phenacylphenanthrolinium bromide (1b) with cyclic
1,3-diketones.
O
O
O
O
O
O
N
O
O
O
O
N
N
O
N
N
O
N
N
O
N
N
N
O
O
O
O
O
5a (69%)
5b (61%) 5c (51%) 6a (74%) 6b (75%)
Scheme 2. The synthetic phenanthroline derivatives 5aec and 6aeb.

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H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
1,4-attractive electrostatic interaction between C1 and C4.20 Such
strong stabilizing effect is unique to Meldrum acids, in a wider
sense, to highly structurally similar substrates like barbituric acid,
thiobarbituric acid, and etc., which have additional a-heteroatom to
two carbonyl groups in the ring. This stabilizing effect would
strongly prevent further O-alkylation because such process re-
quires to disturb such stabilization effect. In contrast, dimedone
and 1,3-cyclohexanedione did not possess such unique effect and,
as a consequence, would allow the O-alkylation reaction to go to get
the oxazabicyclic products. The reactions of N-phenacylphenan-
throlinium salt gave the corresponding oxazabicyclic derivatives 5
and addition products 6 further demonstrated the reality of the
proposed reaction mechanism and generality of this reaction.
In summary an efficient synthetic method for the functionalized
oxazabicyclic compounds form the unprecedented reactions of phe-
nanthrolinium salts having active methylene group with cyclic 1.3-
dicarbonyl compounds was developed. The structure of cyclic
1,3-dicarbonyl compounds plays a key factor for the formation of
C-alkylated products and tandem C-alkylated/intramolecular
O-alkylated oxazabicyclic compounds. Furthermore, we established
the scope and limitation of this reaction, which enabled further
modification that led to molecular diversity. The potential uses of the
reaction in synthetic and medicinal chemistry might quite significant.
3. Experimental section
3.1. Preparation of phenanthrolinium bromides (1aeb)
Fig. 3. The molecular structure of compound 5b.
The solution of phenanthroline (2.0 mmol, 0.396 g) and
p-nitrobenzyl bromide (2.0 mmol, 0.432 g) or
a-phenacyl bromide
(2.0 mmol, 0.398 g) in 20 mL of acetonitrile was stirred at room
temperature for 12 h. The resulting precipitates were collected by
filtration and washed with few acetonitrile to give the product.
3.1.1. N-p-Nitrobenzylphenanthrolinium bromide (1a). White solid,
yield: 90%. Mp 212e214 ꢀC. IR (KBr disc)
n
: 2984 (m), 1603 (m), 1524
(vs), 1465 (w), 1413 (w), 1347 (s), 1245 (w), 1158 (w), 1109 (w), 854
(w), 804 (w) cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 9.85 (d,
;
d
J¼4.8 Hz,1H, ArH), 9.60 (d, J¼7.8 Hz,1H, ArH), 9.09 (s,1H, ArH), 8.76
(d, J¼7.8 Hz,1H, ArH), 8.61 (s, 1H, ArH), 8.50e8.46 (m, 2H, ArH), 8.14
(d, J¼7.2 Hz, 2H, ArH), 7.98 (d, J¼9.6 Hz, 1H, ArH), 7.52 (d, J¼7.8 Hz,
2H, ArH), 7.34 (s, 2H, ArH); 13C NMR (150 MHz, DMSO-d6)
d: 152.2,
149.6, 148.3,146.8, 144.1, 139.0, 137.8, 136.7, 132.9, 131.7,130.8, 127.9,
127.1, 125.4, 125.1, 123.6, 65.5. MS (ESIþ): m/z¼316.24.
3.1.2. N-Phenacylphenanthrolinium bromide (1b). Light yellow
solid, yield: 85%. Mp 208e210 ꢀC. IR (KBr)
n: 2989 (m), 2916 (w),
1688 (vs), 1630 (w), 1589 (w), 1530 (m), 1442 (m), 1350 (m), 1232
(s), 1171 (w), 995 (w), 857 (w) cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
d
: 9.74 (d, J¼4.2 Hz, 1H, ArH), 9.64 (d, J¼7.8 Hz, 1H, ArH), 8.79 (d,
J¼7.2 Hz,1H, ArH), 8.65 (s,1H, ArH), 8.52e8.48 (m, 2H, ArH), 8.46 (s,
1H, ArH), 8.21 (d, J¼6.6 Hz, 2H, ArH), 7.92 (t, J¼3.6 Hz,1H, ArH), 7.85
(t, J¼7.2 Hz, 1H, ArH), 7.75 (t, J¼6.6 Hz, 2H, ArH), 7.36 (s, 2H, ArH);
13C NMR (150 MHz, DMSO-d6)
d: 190.7, 152.0, 148.6, 148.1, 138.4,
138.0, 136.2, 134.3, 134.1, 132.0, 131.4, 130.6, 129.3, 128.1, 127.0,
125.5, 124.8, 69.5. MS (ESIþ): m/z¼299.12.
3.2. The reactions of N-p-nitrobenzylphenanthrolinium
Fig. 4. The molecular structure of compound 6b.
bromide (1a) with cyclic 1,3-dicarbonyl compounds
stabilizing effect of enolate anion, in which the anomeric effect
between the oxygen atom (O5) and the vacant antibonding of the
O3 (the ether)eC4 bond. Lee and co-workers proposed that
deprotonation of Meldrum’s acid would lead to increase of elec-
tron-delocalization of the nonbonding electrons of the carbanion
moiety to the adjacent vacant carbonyl antibonding orbitals and
N-p-Nitrobenzylphenanthrolinium bromide (1.0 mmol, 0.395 g)
and cyclic 1,3-dicarbonyl compound (1.0 mmol) were added to
20 mL of acetonitrile. Then 0.25 mL of triethylamine was added to
the mixture. The mixture was stirred at room temperature for 24 h.
In most cases the resulting precipitates were collected by filtration,
which was recrystallized in ethanol to give the pure products for

H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
2867
O
N
O
N
O
O
O
N
N
N
N
O
N
N
Br
Br
NO2
NO2
NO2
NO2
1a
(A)
(B)
4
- Et3NH+
O
O
+ Et3N
O
O
N
O
O
+ Et3NH+
- Et3N
N
N
N
N
O
N
NO2
NO2
NO2
3
(D)
(C)
Scheme 3. The proposed formation mechanism for the compounds 3 and 4.
analysis. In few cases the solution was concentrated and the
resulting oily solid was titrated with ethanol to give the products.
Compound 3a: White solid, yield: 66%. Mp 178e180 ꢀC. IR (KBr)
2H, ArH), 7.22 (t, J¼7.2 Hz, 1H, ArH), 5.89 (s, 1H, NCH), 5.83 (d,
J¼16.2 Hz, 1H, NCH2), 5.67 (d, J¼15.6 Hz, 1H, NCH2), 4.39 (s, 1H, CH),
2.37 (d, J¼12.6 Hz, 1H, CH2), 2.20 (d, J¼12.6 Hz, 1H, CH2); 13C NMR
n
: 3435 (w), 2935 (m), 2865 (w), 1644 (w), 1615 (vs), 1522 (s), 1458
(m), 1385 (s), 1342 (s), 1306 (w), 1221 (w), 1170 (w), 1107 (m), 1047
(m), 1026 (w), 991 (w), 836 (w) cmꢁ1 1H NMR (600 MHz, DMSO-
d6)
(150 MHz, CDCl3) d: 162.0, 158.3, 152.1, 148.6, 146.8, 139.5, 137.4,
136.6, 131.8, 129.1, 128.3, 127.8, 127.6, 123.8, 123.4, 123.3, 120.4,
119.8, 116.6, 115.2, 104.9, 84.7, 77.3, 77.1, 76.9, 54.4, 28.3, 26.2. MS
(ESIꢁ): m/z¼476.33. Anal. Calcd for C87H19N3O5: C 70.43, H 4.01, N
8.80. Found: C 70.54, H 4.42, N 8.59.
;
d
: 8.56 (s, 1H, ArH), 8.18 (d, J¼8.4 Hz, 1H, ArH), 8.14 (d, J¼8.4 Hz,
2H, ArH), 7.52 (t, J¼9.0 Hz, 3H, ArH), 7.34 (d, J¼7.8 Hz, 2H, ArH), 5.87
(d, J¼16.8 Hz, 1H, CH2), 5.69 (s, 1H, CH), 5.55 (d, J¼16.8 Hz, 1H, CH2),
4.07 (s, 1H, CH), 2.20 (d, J¼17.4 Hz, 1H, CH2), 2.15e2.08 (m, 2H, CH2),
2.05 (d, J¼13.2 Hz, 1H, CH2), 1.94 (t, J¼13.8 Hz, 2H, CH2), 0.98 (s, 3H,
Compound 4a: Light yellow solid, yield: 87%. Mp 219e221 ꢀC. IR
(KBr)
1346 (s), 1271 (w),1230 (w), 1204 (m), 1137 (w), 1106 (w), 1053 (w),
1028 (w), 962 (w), 861 (w), 784 (w) cmꢁ1 1H NMR (600 MHz,
DMSO-d6)
n: 3451 (w), 2992 (w), 1634 (vs), 1525 (m), 1421 (m), 1388 (s),
CH3), 0.84 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d: 196.1,
;
167.6, 148.8, 146.9, 146.5, 139.5, 137.2, 136.5, 129.0, 128.7, 128.6,
127.8, 123.3, 120.1, 119.2, 114.3, 83.8, 54.1, 50.5, 41.7, 32.1, 29.4, 27.4,
26.3, 26.2. MS (ESIþ): m/z¼456.65. Anal. Calcd for C27H25N3O4: C
71.19, H 5.53, N 9.22. Found: C 70.86, H 5.81, N 8.79.
d
: 9.01 (d, J¼7.8 Hz, 1H, ArH), 8.92 (d, J¼2.4 Hz, 1H, ArH),
8.69 (d, J¼6.6 Hz, 1H, ArH), 8.55 (d, J¼7.8 Hz, 1H, ArH), 8.15 (d,
J¼8.4 Hz, 2H, ArH), 8.01 (d, J¼9.0 Hz, 1H, ArH), 7.90 (d, J¼9.0 Hz, 1H,
ArH), 7.82e7.80 (m,1H, ArH), 7.44 (d, J¼8.4 Hz, 2H, ArH), 6.98 (s, 2H,
Compound 3b: White solid, yield: 47%. Mp 136e138 ꢀC. IR (KBr)
CH2), 1.78 (s, 6H, CH3); 13C NMR (150 MHz, DMSO-d6)
d: 137.0, 131.8,
n
: 2948 (w), 1653 (m), 1621 (vs), 1511 (s), 1459 (m), 1389 (m), 1348
(vs),1230 (w), 1187 (w), 1168 (w), 1132 (w), 1115 (m), 1063 (w), 1030
(m), 992 (w), 936 (w), 834 (w) cmꢁ1; 1H NMR (600 MHz, CDCl3)
121.7, 120.2, 120.1, 119.2, 113.1, 110.3, 109.4, 104.2, 102.0, 101.4, 101.1,
99.0, 98.0, 97.3, 95.2, 74.4, 56.2, 36.9. MS (ESIþ): m/z¼458.31. Anal.
Calcd for C25H19N3O6: C 65.64, H 4.19, N 9.19. Found: C 65.28, H
4.33, N 9.30.
d:
8.56 (d, J¼2.4 Hz, 1H, ArH), 8.13 (d, J¼8.4 Hz, 2H, ArH), 8.03 (d,
J¼7.8 Hz, 1H, ArH), 7.72 (d, J¼7.8 Hz, 1H, ArH), 7.57 (d, J¼8.4 Hz, 2H,
ArH), 7.29 (d, J¼7.8 Hz, 1H, ArH), 7.25e7.23 (m, 1H, ArH), 5.78 (d,
J¼16.2 Hz, 1H, NCH), 5.55 (d, J¼17.0 Hz, 2H, NCH2), 4.22 (s, 1H,
NCH), 2.43e2.37 (m, 2H, CH2), 2.28e2.23 (m, 1H, CH2), 2.14e2.08
(m, 2H, CH2), 1.98e1.93 (m, 2H, CH2), 1.88e1.84 (m, 1H, CH2); 13C
Compound 4b: Yellow solid, yield: 61%. Mp 296e298 ꢀC. IR (KBr)
n
: 2926 (w), 1606 (vs), 1521 (s), 1458 (m), 1440 (m), 1424 (m), 1399
(w), 1344 (w), 1276 (w), 1237 (m), 1153 (w), 1103 (w), 840 (w), 800
(w) cmꢁ1 1H NMR (600 MHz, DMSO-d6)
;
d
: 9.07 (d, J¼7.2 Hz, 1H,
ArH), 8.92 (d, J¼3.6 Hz, 1H, ArH), 8.56 (d, J¼7.8 Hz, 1H, ArH), 8.50 (d,
J¼7.2 Hz, 1H, ArH), 8.17 (d, J¼8.4 Hz, 2H, ArH), 7.99e7.90 (m, 2H,
ArH), 7.83e7.81 (m, 1H, ArH), 7.44 (d, J¼8.4 Hz, 2H, ArH), 7.03 (s, 2H,
NMR (150 MHz, CDCl3) d: 196.4, 169.3, 149.0, 146.8, 146.5, 139.5,
137.2, 136.4, 128.9, 128.7, 128.4, 127.9, 123.3, 120.1, 119.2, 115.6, 83.9,
54.3, 36.6, 27.9, 26.4, 26.2, 20.7. MS (ESIꢁ): m/z¼426.33. Anal. Calcd
for C25H21N3O4: C 70.25, H 4.95, N 9.83. Found: C 70.38, H 5.27, N
9.66.
CH2), 3.22 (s, 6H, NCH3); 13C NMR (150 MHz, DMSO-d6)
d: 175.6,
162.3, 161.3, 157.5, 148.1, 146.8, 146.6, 145.3, 139.4, 136.8, 136.1, 131.0,
129.3, 128.3, 127.6, 125.4, 124.5, 124.2, 123.7, 92.9, 63.8, 35.7, 30.7.
MS (ESID): m/z¼470.44. Anal. Calcd for C25H19N5O5: C 63.96, H 4.08,
N 14.92. Found: C 63.83, H 4.37, N 14.56.
Compound 3c: Light yellow solid, yield: 53%. Mp 170e172 ꢀC. IR
n: 2961 (w), 1705 (vs), 1622 (s), 1519 (m), 1458 (m), 1398 (m),
(KBr)
1342 (s), 1228 (w), 1198 (w), 1139 (w), 1102 (m), 1011 (m), 952 (w),
908 (w), 884 (w) cmꢁ1 1H NMR (600 MHz, CDCl3)
: 8.61 (s, 1H,
ArH), 8.08 (d, J¼7.8 Hz, 1H, ArH), 8.04 (d, J¼7.2 Hz, 2H, ArH), 7.83 (d,
J¼7.2 Hz, 1H, ArH), 7.62 (d, J¼7.2 Hz, 1H, ArH), 7.58 (d, J¼7.2 Hz, 2H,
ArH), 7.47 (t, J¼6.6 Hz, 1H, ArH), 7.38 (d, J¼7.8 Hz, 1H, ArH), 7.28 (s,
Compound 4c: Yellow solid, yield: 49%. Mp 244e246 ꢀC. IR (KBr)
;
d
n
: 3403 (w), 3048 (w), 1673 (w), 1663 (m), 1617 (vs), 1524 (s), 1453
(s), 1345 (m), 1276 (w), 1238 (w), 1156 (m), 1100 (w), 851 (w), 801
(w), 775 (w) cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 11.38 (s, 2H,
NH), 9.14 (d, J¼5.4 Hz, 1H, ArH), 8.93 (s, 1H, ArH), 8.58 (d, J¼7.2 Hz,
;
d

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H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
1H, ArH), 8.50 (d, J¼6.0 Hz, 1H, ArH), 8.16 (d, J¼7.8 Hz, 2H, ArH),
8.00 (s, 2H, ArH), 7.83 (t, J¼3.6 Hz, 1H, ArH), 7.46 (d, J¼7.2 Hz, 2H,
2H, CH2), 1.95 (t, J¼6.0 Hz, 2H, CH2); 13C NMR (150 MHz, CDCl3)
d:
196.6, 169.8, 145.4, 136.2, 132.6, 128.6, 127.9, 119.7, 117.8, 115.4, 86.2,
57.5, 36.7, 28.2, 26.5, 26.0, 20.8. MS (ESIþ): m/z¼411.62. Anal. Calcd
for C26H22N2O3: C 76.08, H 5.40, N 6.82. Found: C 75.94, H 5.75, N
6.36.
ArH), 7.04 (s, 2H, NCH2); 13C NMR (150 MHz, DMSO-d6)
d: 175.6,
162.3,161.3,157.5,148.1,146.8,146.6,145.3,139.5,136.8,136.1,130.9,
129.3, 128.3, 127.6, 125.4, 124.5, 124.2, 123.7, 92.9, 63.8, 35.7, 30.7.
MS (ESIþ): m/z¼458.62. Anal. Calcd for C23H15N5O4S: C 60.39, H
3.31, N 15.31. Found: C 60.47, H 3.69, N 15.06.
Compound 5c: Light yellow solid, yield: 51%. Mp 168e170 ꢀC. IR
(KBr)
1399 (s), 1361 (w), 1329 (w), 1305 (m), 1229 (m), 1125 (w), 1101 (w),
1042 (w), 1020 (m), 963 (w), 832 (w), 759 (w) cmꢁ1 1H NMR
(600 MHz, CDCl3)
: 8.03 (d, J¼6.6 Hz, 2H, ArH), 7.95 (d, J¼4.8 Hz,
n: 2971 (w), 1703 (vs), 1626 (s), 1572 (w), 1500 (w), 1465 (s),
Compound 4d: Light yellow solid, yield: 81%. Mp 288e290 ꢀC. IR
(KBr)
1454 (s), 1425 (s), 1398 (m), 1346 (s), 1287 (w), 1241 (m), 1222 (m),
1194 (w), 1133 (w), 1106 (w), 1014 (w), 985 (w), 862 (w) cmꢁ1 1H
NMR (600 MHz, DMSO-d6)
: 9.99 (d, J¼7.2 Hz, 1H, ArH), 8.90 (d,
n
: 3024 (w), 2912 (w), 1656 (w), 1573 (vs), 1534 (s), 1520 (s),
;
d
;
2H, ArH), 7.80e7.77 (m, 2H, ArH), 7.62 (t, J¼6.0 Hz, 1H, ArH), 7.53 (t,
J¼6.6 Hz, 2H, ArH), 7.48 (t, J¼7.2 Hz, 1H, ArH), 7.28 (d, J¼7.8 Hz, 1H,
ArH), 7.24 (d, J¼7.8 Hz, 2H, ArH), 7.07 (d, J¼3.6 Hz, 1H, ArH), 6.23 (s,
1H, NCH), 5.88 (d, J¼17.4 Hz, 1H, NCH2), 4.96 (d, J¼17.4 Hz, 1H,
NCH2), 4.40 (s, 1H, CH), 2.44e2.36 (m, 2H, CH2); 13C NMR (150 MHz,
d
J¼3.0 Hz, 1H, ArH), 8.60e8.56 (m, 2H, ArH), 8.18e8.14 (m, 3H, ArH),
7.96 (d, J¼9.0 Hz, 1H ArH), 7.82e7.80 (m, 1H, ArH), 7.42 (d, J¼9.0 Hz,
2H, ArH), 6.97 (s, 2H, CH2), 2.44 (s, 2H, CH2), 1.05 (t, J¼6.6 Hz, 2H,
CH2). MS (ESIꢁ): m/z¼410.42. Anal. Calcd for C24H17N3O4: C 70.07, H
4.16, N 10.21. Found: C 69.72, H 4.50, N 9.87.
CDCl3) d: 162.2, 158.7, 152.1, 145.5, 138.5, 137.0, 136.5, 136.2, 132.7,
131.6,129.0,128.7,127.9,127.5,125.7,123.8,122.6,120.0,118.3,116.6,
115.7, 104.9, 86.9, 57.2, 28.4, 25.9. MS (ESIþ): m/z¼461.53. Anal.
Calcd for C29H20N2O4: C 75.64, H 4.38, N 6.08. Found: C 75.58, H
4.77, N 5.64.
Compound 4e: Yellow solid, yield: 43%. Mp 240e242 ꢀC. IR (KBr)
n
: 2927 (w), 2853 (w), 1695 (s), 1641 (vs), 1603 (s), 1513 (m), 1493
(s), 1446 (w), 1424 (w), 1343 (m), 1322 (w), 1250 (w), 1228 (w), 1164
(w),1132 (w), 967 (w), 861 (w) cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
Compound 6a: Red solid, yield: 74%. Mp 228e230 ꢀC. IR (KBr)
n:
d
: 11.67 (s, 1H, NH), 8.78 (s, 1H, ArH), 8.56 (d, J¼6.0 Hz, 1H, ArH),
2994 (w), 1651 (m), 1597 (w), 1542 (m), 1517 (vs), 1314 (s), 1371 (w),
1340 (s), 1273 (s), 1232 (m), 1187 (m), 1156 (m), 1028 (w), 1005 (w),
8.41 (d, J¼7.2 Hz, 1H, ArH), 8.12 (d, J¼4.8 Hz, 3H, ArH), 7.87 (d,
J¼6.6 Hz, 1H, ArH), 7.74 (d, J¼5.4 Hz, 1H, ArH), 7.64 (t, J¼4.2 Hz, 1H,
ArH), 7.43 (d, J¼6.6 Hz, 2H, ArH), 6.47 (s, 2H, NCH2); 13C NMR
936 (w), 848 (w) cmꢁ1 1H NMR (600 MHz, CDCl3)
; d: 8.36 (s, 1H,
ArH), 8.23 (d, J¼8.4 Hz, 1H, ArH), 8.10 (d, J¼6.6 Hz, 1H, ArH), 8.06 (d,
J¼9.0 Hz, 2H, ArH), 8.00 (s, 1H, ArH), 7.96 (d, J¼6.6 Hz, 2H, ArH),
7.67 (d, J¼8.4 Hz, 2H, ArH), 7.41 (s, 2H, ArH), 7.32 (s, 2H, CH2),1.69 (s,
6H, CH3). MS (ESIþ): m/z¼441.21. Anal. Calcd for C26H20N2O5: C
70.90, H 4.58, N 6.36. Found: C 70.59, H 4.81, N 6.17.
(150 MHz, DMSO-d6) d: 168.0, 166.1, 148.0, 147.3, 146.3, 142.0, 140.5,
139.0, 136.6, 136.5, 129.4, 127.3, 123.9, 123.6, 123.4, 123.2, 120.9,
109.6, 95.8, 60.2. MS (ESIꢁ): m/z¼429.26. Anal. Calcd for
C22H14N4O4S: C 61.39, H 3.28, N 13.02. Found: C 61.23, H 3.65, N
12.74.
Compound 6b: Yellow solid, yield: 75%. Mp 254e256 ꢀC. IR (KBr)
n
: 3668 (w), 3143 (w), 1695 (s), 1641 (vs), 1513 (m), 1445 (s), 1342
(m), 1320 (m), 1227 (w), 1162 (w), 1131 (w), 826 (w), 705 (w) cmꢁ1
1H NMR (600 MHz, DMSO-d6)
3.3. The reactions of N-phenacylphenanthrolinium bromide
(1b) with cyclic 1,3-dicarbonyl compounds
;
d
: 8.25 (d, J¼7.2 Hz, 1H, ArH), 8.14 (d,
J¼7.2 Hz, 2H, ArH), 7.81 (t, J¼7.2 Hz, 1H, ArH), 7.63 (s, 1H, ArH),
7.57e7.52 (m, 2H, ArH), 7.43 (d, J¼9.6 Hz, 1H, ArH), 7.34 (s, 3H, ArH),
7.23 (d, J¼7.8 Hz, 2H, ArH), 7.05 (s, 1H, NCH2), 1.22 (s, 2H, CH2), 0.89
N-Phenacylphenanthrolinium bromide (1.0 mmol, 0.378 g) and
cyclic 1,3-dicarbonyl compound (1.0 mmol) were added to 20 mL of
acetonitrile. Then 0.25 mL of triethylamine was added to the mix-
ture. The mixture was stirred at room temperature for 24 h. In most
cases the resulting precipitates were collected by filtration, which
was recrystallized in ethanol to give the pure products for analysis.
In few cases the solution was concentrated and the resulting oily
solid was titrated with ethanol to give the products.
(s, 2H, CH2); 13C NMR (150 MHz, DMSO-d6)
d: 175.6, 162.3, 161.3,
157.5, 148.1, 146.6, 145.3, 139.5, 136.8, 136.1, 130.9, 129.3, 128.3,
127.6, 125.4, 124.5, 124.2, 123.7, 92.9, 63.8, 35.7, 30.8. MS (ESIꢁ): m/
z¼393.40. Anal. Calcd for C25H18N2O3: C 76.13, H 4.60, N 7.10.
Found: C 75.74, H 4.90, N 6.75.
Compound 5a: White solid, yield: 69%. Mp 164e166 ꢀC. IR (KBr)
4. Supplementary data
n
: 3057 (w), 2955 (w), 2886 (w), 1689 (m), 1646 (m), 1614 (vs), 1507
(w), 1465 (s), 1384 (s), 1329 (m), 1305 (m), 1229 (s), 1173 (w), 1147
Crystallographic data (3a: CCDC 804663; 3c: CCDC 804662; 4a:
CCDC 804661; 5b: CCDC 804664; 6b: CCDC 804660) have been
deposited at the Cambridge Crystallographic Database Centre.
(s), 1115 (w), 1046 (m), 995 (w), 835 (w) cmꢁ1; 1H NMR (600 MHz,
CDCl3)
d
: 8.04 (d, J¼7.2 Hz, 2H, ArH), 7.99 (s, 1H, ArH), 7.93 (d,
J¼8.4 Hz, 1H, ArH), 7.66 (d, J¼7.8 Hz, 1H, ArH), 7.61 (t, J¼7.2 Hz, 1H,
ArH), 7.53 (t, J¼6.6 Hz, 2H, ArH), 7.17 (d, J¼7.8 Hz, 1H, ArH), 7.06 (t,
J¼3.6 Hz, 1H, ArH), 5.87 (s, 1H, NCH), 5.73 (d, J¼17.4 Hz, 1H, NCH2),
7.13 (d, J¼17.4 Hz, 1H, NCH2), 4.25 (s, 1H, CH), 2.27 (s, 2H, CH2), 2.20
(d, J¼9.6 Hz, 2H, CH2), 2.15 (s, 2H, CH2), 1.08 (s, 3H, CH3), 0.99 (s, 3H,
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 20972132).
CH3); 13C NMR (150 MHz, CDCl3)
d: 196.3, 168.1, 145.3, 138.6, 137.0,
136.6, 136.2, 132.6, 128.6, 127.9, 127.7, 127.2, 119.7, 117.8, 114.1, 86.3,
57.4, 50.6, 42.0, 32.3, 29.5, 27.4, 26.4, 26.0. MS (ESIþ): m/z¼439.54.
Anal. Calcd for C28H26N2O3: C 76.69, H 5.98, N 6.39. Found: C 76.41,
H 6.30, N 6.11.
References and notes
€
€
1. (a) Krohnke, F. Angew. Chem., Int. Ed. Engl. 1963, 2, 225; (b) Krohnke, F.; Zecher,
W. Angew. Chem., Int. Ed. Engl. 1962, 1, 626.
2. (a) Tsuge, O.; Kanemasa, S.; Takenaka, S. Bull. Chem. Soc. Jpn. 1985, 58, 3137; (b)
Kojima, S.; Fujitomo, K.; Shinohara, Y.; Shimizu, M.; Ohkata, K. Tetrahedron Lett.
2000, 41, 9847; (c) Kojima, S.; Hiroikea, K.; Ohkata, K. Tetrahedron Lett. 2004, 45,
3565.
Compound 5b: White solid, yield: 61%. Mp 170e172 ꢀC. IR (KBr)
n
: 2947 (w), 1692 (s), 1644 (s), 1609 (vs), 1508 (w), 1468 (s), 1387 (s),
1363 (m), 1330 (w), 1305 (w), 1228 (m), 1190 (w), 1151 (w),1119 (m),
1028 (m), 974 (m), 834 (w), 793 (w) cmꢁ1 1H NMR (600 MHz,
CDCl3)
3. (a) Vo, N. N.; Eyermann, C. J.; Hodge, C. N. Tetrahedron Lett. 1997, 38, 7951; (b)
Neve, F.; Crispini, A.; Campagna, S. Inorg. Chem. 1997, 36, 6150; (c) MacGillivray,
L. R.; Diamente, P. R.; Reid, J. L.; Ripmeester, J. A. Chem. Commun. 2000, 359; (d)
Yamada, S.; Yamamoto, J.; Ohta, E. Tetrahedron Lett. 2007, 48, 855.
;
d
: 8.03 (t, J¼8.4 Hz, 3H, ArH), 7.93 (d, J¼8.4 Hz, 1H, ArH), 7.69
(d, J¼7.8 Hz, 1H, ArH), 7.61 (t, J¼7.2 Hz, 1H, ArH), 7.53 (t, J¼7.2 Hz,
2H, ArH), 7.18 (d, J¼7.8 Hz,1H, ArH), 7.05 (d, J¼4.2 Hz,1H, ArH), 5.86
(s, 1H, NCH), 5.74 (d, J¼17.4 Hz, 1H, NCH2), 5.19 (d, J¼17.4 Hz, 1H,
NCH2), 4.24 (s, 1H, CH), 2.46e2.26 (m, 4H, CH2), 2.15 (t, J¼12.6 Hz,
€
4. (a) Krohnke, F. Synthesis 1976, 1; (b) Ulrich, G.; Ziessel, R. J. Org. Chem. 2004, 69,
2070; (c) Yam, V. W. W.; Wong, K. M. C.; Zhu, N. Angew. Chem., Int. Ed. 2003, 42,
1400; (d) Coppo, P.; Duati, M.; Kozhevnikov, V. N.; Hofstraat, J. W.; De Cola, L.
Angew. Chem., Int. Ed. 2005, 44, 1806.

H. Li, C.-G. Yan / Tetrahedron 67 (2011) 2863e2869
2869
€
5. (a) Pabst, G. R.; Pfuller, O. C.; Sauer, J. Tetrahedron 1999, 55, 5047; (b) Hovinen,
41, 3847; (e) Yue, G.; Wan, Y.; Song, S.; Yang, G.; Chen, Z. Bioorg. Med. Chem.
2005, 15, 453; (f) Takamura, M.; Funabashi, K.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 2000, 122, 6327.
J.; Hakala, H. Org. Lett. 2001, 3, 2473; (c) Kozhevnikov, V. N.; Kozhevnikov, D. M.;
Nikitina, T. V.; Rusinov, V. L.; Chupakhin, O. N.; Zabel, M.; Konig, B. J. Org. Chem.
€
2003, 68, 2882; (d) Constable, E. C.; Edwards, A. J.; Raithby, P. R.; Soto, J.;
Tendero, M. J. L.; Martínez-Manez, R. Polyhedron 1995, 14, 3061; (e) Lai, S. W.;
13. (a) Yan, C. G.; Cai, X. M.; Wang, Q. F.; Wang, T. Y.; Zheng, M. Org. Biomol. Chem.
2007, 5, 945; (b) Yan, C. G.; Song, X. K.; Wang, Q. F.; Sun, J.; Siemeling, U.; Bruhn,
C. Chem. Commun. 2008, 1440; (c) Wang, Q. F.; Song, X. K.; Chen., J.; Yan, C. G. J.
Comb. Chem. 2009, 11, 1007; (d) Wang, Q. F.; Hou, H.; Hui, L.; Yan, C. G. J. Org.
Chem. 2009, 74, 7403; (e) Yan, C. G.; Wang, Q. F.; Song, X. K.; Sun, J. J. Org. Chem.
2009, 74, 710; (f) Wang, Q. F.; Hui, L.; Hou, H.; Yan, C. G. J. Comb. Chem. 2010, 12,
260; (g) Han, Y.; Chen, J.; Hui, L.; Yan, C. G. Tetrahedron 2010, 66, 7743.
14. (a) Bencinia, A.; Lippolisb, V. Coord. Chem. Rev. 2010, 254, 2096; (b) O’Neill, D. J.;
Helquist, P. Org. Lett. 1999, 1, 1659; (c) Maghsoodlou, M. T.; Marandi, M.; Hazeri,
N.; Aminkhani, A.; Kabiric, R. Tetrahedron Lett. 2007, 48, 3197.
15. Ullah, E.; Rotzoll, S.; Schmidt, A.; Michalikc, D.; Langer, P. Tetrahedron Lett. 2005,
46, 8997.
16. (a) Moghaddam, F. M.; Mirjafary, Z.; Saeidian, H.; Taheri, S.; Doulabi, M.; Kia-
mehr, M. Tetrahedron 2010, 66, 134; (b) Moghaddam, F. M.; Taheri, S.; Mirjafary,
Z.; Saeidian, H. Synlett 2010, 123.
17. (a) Wang, J. F.; Liao, Y. X.; Kuo, P. Y.; Gau, Y. H.; Yang, D. Y. Synlett 2006, 2791; (b)
Lai, J. T.; Kuo, P. Y.; Gau, Y. H.; Yang, D. Y. Tetrahedron Lett. 2007, 48, 7796; (c) Lai,
J. T.; Yang, Y. J.; Lin, J. H.; Yang, D. Y. Synlett 2010, 111.
18. (a) Yang, D. H.; Chen, Y. S.; Kuo, P. Y.; Lai, J. T.; Jiang, C. M.; Lai, C. H.; Liao, Y. H.;
Chou, P. T. Org. Lett. 2007, 9, 5287; (b) Lai, J. T.; Shieh, P. S.; Huang, W. H.; Yang,
D. H. J. Comb. Chem. 2008, 10, 381; (c) Lin, C. H.; Jhang, J. F.; Yang, D. H. Org. Lett.
2009, 11, 4064; (d) Lin, C. H.; Chen, J. L.; Yang, D. H. J. Comb. Chem. 2010, 12, 119.
19. (a) Moghaddam, F. M.; Mirjafary, M.; Saeidian, H.; Taheri, S.; Soltanzadeh, B.
Tetrahedron 2010, 66, 3678; (b) Moghaddam, F. M.; Mirjafary, Z.; Saeidian, H.;
Taheri, S.; Khodabakhshi, M. R. Tetrahedron Lett. 2010, 51, 2704.
ꢀꢀ
Chan, M. C. W.; Cheung, K. K.; Che, C. M. Inorg. Chem. 1999, 38, 4262.
6. (a) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A.
Acc. Chem. Res. 1996, 29, 123; (b) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000,
39, 3168; (c) Bora, U.; Saikia, A.; Boruah, R. C. Org. Lett. 2003, 5, 435; (d) Xia, Z.
Q.; Przewloka, T.; Koya, K.; Ono, M.; Chen, S. J.; Sun, L. J. Tetrahedron Lett. 2006,
47, 8817.
7. (a) Katritzky, A. R.; Grzeskowiak, N. E.; Alvarez-Buila, J. J. Chem. Soc., PerkinTrans.1
1981, 1180; (b) Druta, I. I.; Dinica, R. M.; Bacu, E.; Humelnicu, I. Tetrahedron 1998,
54,10811; (c) Dinica, R. M.; Druta, I. I.; Pettinari, C. Synlett 2000, 7,1013; (d) Furdui,
B.; Dinica, R.; Druta, I. I.; Demeunynck, M. Synthesis 2006, 16, 2640.
8. (a) Peng, W. M.; Zhu, S. Z. J. Chem. Soc., Perkin Trans. 1 2001, 3204; (b) Hu, J. X.;
Jiang, X.; He, T.; Zhou, J.; Hu, Y. F.; Hu, H. W. J. Chem. Soc., Perkin Trans. 1 2001,
1820; (c) Zhang, X. C.; Huang, W. Y. Synthesis 1999, 1, 51; (d) Wu, K.; Chen, Q. Y.
Synthesis 2003, 35.
9. Kojima, S.; Suzuki, M.; Watanabe, A.; Ohkata, K. Tetrahedron Lett. 2006, 47, 9061.
10. Chuang, C. P.; Tsai, A. I. Synthesis 2006, 4, 675.
ꢀ
ꢀ
ꢀ
}
11. (a) Toth, J.; Dancso, A.; Blasko, G.; Toke, L.; Groundwater, P. W.; Nyerges, M.
Tetrahedron 2006, 62, 5725; (b) Muthusaravanan, S.; Perumal, S.; Yogeeswari, P.;
Sriram, D. Tetrahedron Lett. 2010, 51, 6439; (c) Voskressensky, L. G.; Kulikova, L.
N.; Listratova, A. V.; Borisov, R. S.; Kukaniev, M. A.; Varlamov, A. V. Tetrahedron
Lett. 2010, 51, 2269.
12. (a) Yavari, I.; Mirzaei, A.; Moradi, L.; Hosseini, N. Tetrahedron Lett. 2008, 49,
2355; (b) Paira, P.; Hazra, A.; Sahu, K. B.; Banerjee, S.; Mondal, N. B.; Sahu, N.
P.; Weber, M.; Luger, P. Tetrahedron 2008, 64, 4026; (c) Liu, Y.; Hu, H. Y.; Liu,
Q. J.; Hu, H. W.; Xu, J. H. Tetrahedron 2007, 63, 2024; (d) Fakhfakh, M. A.;
Franck, X.; Fournet, A.; Hocquemiller, R.; Figadere, B. Tetrahedron Lett. 2001,
20. (a) Byun, K.; Mo, Y. R.; Gao, J. L. J. Am. Chem. Soc. 2001, 123, 3974; (b) Nakamura,
S.; Hirao, H.; Ohwada, T. J. Org. Chem. 2004, 9, 4309; (c) Lee, I.; Han, I. S.; Kim, C.
K.; Lee, H. W. Bull. Korean Chem. Soc. 2003, 24, 1141.