Otherwise inert reaction of sulfonamides/carboxamides with formamides via proton transfer-enhanced reactivity

Article abstract of DOI:10.1039/c3ob27351b

NBS-mediated addition-elimination reaction of sulfonamides/carboxamides and formamides afforded N-sulfonylamidines and N-formylarylamides, respectively, depending on the different mechanism of elimination. Hydrogen bond-induced proton transfer leads to en

Full text of DOI:10.1039/c3ob27351b

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Otherwise inert reaction of sulfonamides/
carboxamides with formamides via proton
transfer-enhanced reactivity†
Cite this: DOI: 10.1039/c3ob27351b
Zaihai Niu,a Shaoxia Lin,a Zhiyong Dong,a Hao Sun,a Fushun Liang*a,b and
Jingping Zhang*a
NBS-mediated addition–elimination reaction of sulfonamides/carboxamides and formamides afforded
N-sulfonylamidines and N-formylarylamides, respectively, depending on the different mechanism of elimi-
nation. Hydrogen bond-induced proton transfer leads to enhanced reactivities and was proposed as the
key driving force for the reaction to take place. The protocol demonstrates the possibility of constructing
chemical bonds based on a proton transfer strategy induced by noncovalent hydrogen bond interaction.
Received 4th December 2012,
Accepted 10th February 2013
DOI: 10.1039/c3ob27351b
www.rsc.org/obc
reactivity and was proposed as the key driving force for the
reaction to take place in this work (Scheme 1).
Introduction
As well known noncovalent interactions, hydrogen bonding1
The initial investigation started from 4-methylbenzenesulfon-
has found vast applications in areas such as molecular recog- amide (1a) and N,N-dimethylformamide8 (2a). Generally, the
nition, crystal engineering, and biological systems.2 Recently, reaction between them is quite difficult, due to their inherent
organic catalysis via noncovalent weak interactions has low reactivities (Scheme 1a). However, in our study, we found
attracted increasing interest from synthetic chemists.3 For that the reaction between 1a and 2a (both as reactant and
instance, Schreiner and Wittkopp reported
complex of an N-acyloxazolidinone with an N,N′-disubstituted amidine 3a as
a
H-bonded solvent, 2.0 mL) did take place at 120 °C, affording N-sulfonyl
single product in reproducible yield
a
electron-poor thiourea and used it in Diels–Alder reactions.4 (Scheme 1b). The reason for such an unusual reaction to occur
Jacobsen and co-workers developed hydrogen bond activation may be explained as hydrogen bond activation (Scheme 1c),
of benzhydryl bromide by anion binding to the benzhydryl which leads to simultaneously increased nucleophilicity for
cations formed.5 Zhang et al. reported C–N bond cleavage of TsNH2 and electrophilicity for DMF.9–11 Consequently, direct
allylic amines via hydrogen bond activation with alcohol sol-
vents in Pd-catalyzed allylic alkylation.6 Thus, the exploration
of hydrogen bond activation in organic synthesis is an extre-
mely appealing yet challenging goal.
Results and discussion
In our research on halogen (e.g. halogenation, halonium,
hypervalent halogen and halogen bond) mediated organic
reactions,7 we would like to communicate here an otherwise
inert reaction of sulfonamides/carboxamides with formamides
leading to amidines and N-formylamides. Proton transfer
induced by hydrogen bond interaction led to enhanced
aDepartment of Chemistry, Northeast Normal University, Changchun 130024, China.
E-mail: liangfs112@nenu.edu.cn; Fax: (+86) 431-85099759
bKey Laboratory for UV-Emitting Materials and Technology of Ministry of Education,
Northeast Normal University, Changchun 130024, China
†Electronic supplementary information (ESI) available: Experimental details and
characterization for all new compounds. See DOI: 10.1039/c3ob27351b
Scheme 1 Initial investigation.
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Table 2 NBS-mediated reactions of arylsulfonamides and formamidesa,b
Scheme 2 Proton transfer promoted by halogen activated hydrogen bond
interaction.
addition was achieved, along with the subsequent elimination
of water, to give 3a, although in modest yield.
Encouraged by the preliminary results and with the aim of
increasing the product yield and lowering the temperature,
we subsequently sought a halogen activator to do this reaction
(Scheme 2). The role of the halogen activator is to make TsNH2
a stronger H-donor by the formation of TsNHBr,12,13 and
further reinforce the hydrogen bond interaction with DMF.4 To
our delight, with readily available NBS as the halogen source,
the reaction of 1a in anhydrous DMF (2a) proceeded at 80 °C,
giving 3a in 63% yield (Table 1, entry 1). It was found that the
addition of trace amounts of water can further increase the
yield to 89% (entries 2–4), which is consistent with the mecha-
nism proposed afterward. In addition to NBS, NIS and DIB
exhibited similar reactivity, while NCS gave lower efficiency
(entries 5–7). The screening of other solvents like toluene,
THF, MeNO2 and MeCN gave unsatisfactory results
(entries 8–11). Thus, in the following work, anhydrous DMF
was used as the solvent with the addition of 0.2 equiv. of
water, and commercially available and inexpensive NBS was
selected as the halogen source.
a Reaction conditions: 1 (1.0 mmol), 2 (2.0 mL), NBS (1.1 equiv.) and
H2O (0.2 equiv.) at 80 °C for 5–6 h. b Yield of isolated product.
Thus, a variety of substituted sulfonamides including aryl-
sulfonamides and heteroarylsulfonamides were subjected to
the reaction conditions (Table 2). All the reactions with DMF
proceeded efficiently, giving N-sulfonylamidines 3b–h in
61–91% yield. Additionally, reactions with other formamides
like N,N-diethylformamide and morpholine-4-carbaldehyde
also proceeded smoothly, and the corresponding products 3i
and 3j were attained, albeit in low to moderate yields.14
Amidine derivatives have been widely used in medicinal chem-
istry, as well as being key intermediates in organic synthesis.15
The protocol provides a straightforward and efficient entry to
N-sulfonyl amidines of type 3.
In order to further explore the halogen-mediated reaction
developed here and its utility in organic synthesis, arylcarbox-
amides were investigated in the following work. As a result,
reactions activated by NBS proceeded smoothly at 80 °C, and a
variety of N-formylated products 5a–g were produced in
26–58% yield (Table 3).16 Such a transformation demonstrates
an alternative mild N-formylation method.17
Table 1 Optimization of the reaction conditionsa
Entry
X+
Solvent
H2O (equiv.)
Yieldb (%)
Computational calculation was conducted with the aim of
understanding the role of halogen in the reaction and the
possible mechanism. Fig. 1 shows the structures of intermedi-
ates and transition states 6–8 involved in the transformation.
One can clearly observe the formation of an N–H⋯O hydrogen
bond (H⋯O distance 1.78 Å; N⋯C distance 3.51 Å) in 6 and
subsequent proton transfer from arylsulfonamide to DMF
(H⋯O distance 0.99 Å; N⋯C distance 2.52 Å) to give transition
state 7, which causes significant charge density redistribution
on the nitrogen atom of the sulfonylamide and the carbonyl
carbon atom of DMF (see the ESI† for details). Intermediate 8
corresponds to the structure of the resulting C–N adduct.18
On the basis of all the results described above, the possible
mechanism for the reaction of sulfonamide/carboxamide and
1
2
3
4
5
6
7
8
NBS
NBS
NBS
NBS
NIS
NCS
DIB
NBS
NBS
NBS
NBS
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Toluene
THF
—
63
77
88
89
89
41
88
76
<5
33
52
1.0
0.5
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
9
10
11
MeNO2
MeCN
a Reaction conditions: 1a (1.0 mmol), NBS (1.1 equiv.), H2O (x equiv.) in
anhydrous DMF (2.0 mL) at 80 °C for 7.5 h (entries 1–7). 1a
(1.0 mmol), 2a (2.0 equiv.), NBS (1.1 equiv.), H2O (0.2 equiv.) in
anhydrous solvent (2.0 mL) at 80 °C for 7.5 h (entries 8–11). b Isolated
yield.
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electrophilicity for DMF.11 Obviously, dual activation of the
two types of substrates was achieved via proton transfer
induced by the hydrogen bond interaction. As a result, direct
C–N bond formation furnishes the adduct V. Hydrolysis of
V generates acetal VI. Finally, amidines 3 are produced upon
elimination of water for sulfonamide substrates 1. For carbox-
amide substrates 4, N-formylation products 5 are attained via
elimination of dimethylamine. The protocol demonstrates the
possibility of constructing chemical bonds by a proton transfer
strategy induced by noncovalent hydrogen bond interaction. It
was noteworthy that both N-sulfonylamidine and N-formylaryl-
amide products were prepared in modest to high yields, which
is inferior to the results reported by Wan and co-workers.19
This is most probably due to the existence of the equilibrium
in the proton transfer process (II → III → IV → V). Compu-
tational calculation indicates a high energy barrier in this step
(see the ESI†). The subsequent hydrolysis and elimination of
water or dimethylamine (V → VI → 3/5) lead to the final
compounds.
Table 3 NBS-mediated reactions of arylcarboxamides and DMFa,b
a Reaction conditions: 4 (1.0 mmol), 2a (2.0 mL), NBS (1.1 equiv.) and
H2O (0.2 equiv.) at 80 °C for 5–6 h. b Isolated yield.
Conclusion
In conclusion, we have reported, for the first time, NBS-
mediated addition–elimination of sulfonamides/carboxamides
and formamides. The reaction afforded N-sulfonylamidines
and N-formylarylamides, respectively, depending on the type
of elimination. The simple and straightforward approach not
only provides a synthetic method toward N-sulfonylamidines
and N-formylamides, but also illustrates the possibility
and potential of non-covalent hydrogen bond-induced proton
transfer as a complementary strategy for chemical bond for-
mation. Further work on hydrogen bond activation and its
application in organic synthesis is underway in our laboratory.
Fig. 1 Selected structures of intermediates and transition states 6–8 (left to
right).
Experimental
General methods
All reagents were purchased from commercial sources and
used without treatment, unless otherwise indicated. The pro-
ducts were purified by column chromatography over silica gel.
1H NMR and 13C NMR spectra were recorded at 25 °C on a
Varian 500 MHz and 125 MHz, respectively, using TMS as
internal standard. Elemental analyses were measured on an
E-2400 analyzer (Perkin-Elmer). Mass spectra were recorded on
an Agilient 1100 LCMsD mass spectrometer.
Scheme 3 Proposed halogen activated hydrogen bond induced proton trans-
fer mechanism.
General procedure for the preparation of 3 and 5 (3a as an
example). To a solution of 4-methylbenzenesulfonamide 1a
(171 mg, 1.0 mmol) in DMF (2 mL) was added NBS (196 mg,
DMF is depicted in Scheme 3. The reaction of sulfonylamide/ 1.1 mmol) and water (3.6 μL). The mixture was stirred at 80 °C.
carboxamide with NBS yields N-bromosulfonamide or N-bromo- After the starting material 1a was consumed as indicated
carboxamide (I).12 The hydrogen bond interaction between by TLC, the reaction mixture was cooled to room temperature
intermediate I and DMF gives rise to asymmetric hydrogen and poured into water and then extracted with CH2Cl2
bond adducts II and III.10 Furthermore, ion pair IV is proposed (3 × 10 mL). The combined organic phase was washed with
to be generated with enhanced nucleophilicity for TsNH2 and water (3 × 10 mL), dried over anhydrous MgSO4, filtered and
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concentrated under reduced pressure. The crude product was (m, 3H), 8.10 (s, 1H), 8.12–8.14 (t, J = 6.5 Hz, 2H). 13C NMR
purified by flash chromatography (silica gel, petroleum ether : (CDCl3, 125 MHz, ppm): 35.5, 41.5, 52.9, 128.5, 129.0, 130.5,
ether = 1 : 2) to give 3a (198 mg, 88%) as a white solid.
131.6, 131.6, 140.2, 160.7, 168.4; MS calcd m/z 270.30, found
271.30 [(M + 1)]+. Anal. Calcd for C11H14N2O4S: C, 48.88;
H, 5.22; N, 10.36; Found: C, 48.99; H, 5.26; N, 10.27%.
Physical data of compounds isolated
N,N-Dimethyl-N′-tosylformimidamide (3a). White solid,
N′-(5-Bromothiophen-2-ylsulfonyl)-N,N-dimethylformimid-
m.p. 134–136 °C. H NMR (CDCl3, 500 MHz, ppm): δ = 2.40 (s, amide (3h). White solid, m.p. 102–104 °C. 1H NMR (CDCl3,
3H), 3.01 (s, 3H), 3.13 (s, 3H), 7.25–7.27 (d, J = 9.5 Hz, 2H), 500 MHz, ppm): δ = 3.06 (s, 3H), 3.17 (s, 3H), 7.00–7.01 (d, J =
7.77–7.78 (d, J = 8.5 Hz, 2H), 8.13 (s, 1H). 13C NMR (CDCl3, 4.0 Hz, 1H), 7.33–7.34 (d, J = 4.0 Hz, 1H), 8.11 (s, 1H). 13C
125 MHz, ppm): 21.4, 35.5, 41.4, 126.4, 129.3, 139.4, 142.4, NMR (CDCl3, 125 MHz, ppm): 35.7, 41.7, 118.4, 130.0, 130.5,
159.0; MS calcd m/z 226.08, found 227.08 [(M + 1)]+. Anal. 145.0, 159.4; MS calcd m/z 297.19, found 298.19 [(M + 1)]+.
Calcd for C10H14N2O2S: C, 53.08; H, 6.24; N, 12.38; Found: Anal. Calcd for C7H9BrN2O2S2: C, 28.29; H, 3.05; N, 9.43;
1
C, 53.29; H, 6.26; N, 12.43%.
Found: C, 28.50; H, 3.09; N, 9.59%.
N,N-Dimethyl-N′-(o-tolylsulfonyl)formimidamide (3b). Yel-
N,N-Diethyl-N′-tosylformimidamide (3i). Yellow solid, m.p.
lowish oil. H NMR (CDCl3, 500 MHz, ppm): δ = 7.85–7.83 (d, 69–71 °C. 1H NMR (CDCl3, 500 MHz, ppm): δ = 1.13–1.16 (t, J =
J = 8.5 Hz, 2H), 7.32–7.30 (d, J = 8.0 Hz, 2H), 3.70 (s, 2H), 7.0 Hz, 3H), 1.24–1.27 (q, J = 7.3 Hz, 3H), 3.36–3.39 (m, 2H),
3.29–3.27 (t, J = 5.5 Hz, 2H), 2.43 (s, 3H), 1.70–1.68 (t, J = 3 Hz, 3.45–3.48 (m, 2H), 7.25–7.27 (d, J = 9.5 Hz, 2H), 7.76–7.78 (d,
4H), 1.55–1.53 (d, J = 5.5 Hz, 2H); 13C NMR (CDCl3, 125 MHz, J = 8.5 Hz, 2H), 8.15 (s, 1H). 13C NMR (CDCl3, 125 MHz, ppm):
ppm): δ = 191.6, 165.6, 145.8, 130.7, 129.63, 129.59, 46.9, 42.0, 12.1, 14.5, 21.5, 40.1, 47.0, 126.3, 129.2, 139.7, 142.3, 158.0;
26.1, 25.4, 24.3, 21.8; MS calcd m/z 231.1, found 232.1 [(M + MS calcd m/z 254.35, found 255.35 [(M + 1)]+. Anal. Calcd for
1)]+. Anal. Calcd for C14H17NO2: C, 72.70; H, 7.41; N, 6.06; C12H18N2O2S: C, 56.67; H, 7.13; N, 11.01; Found: C, 56.88;
1
Found: C, 72.79; H, 7.40; N, 6.05%.
H, 7.19; N, 11.22%.
N,N-Dimethyl-N′-(phenylsulfonyl)formimidamide (3c). White
4-Methyl-N-(morpholinomethylene)benzenesulfonamide (3j).
solid, m.p. 128–129 °C. H NMR (CDCl3, 500 MHz, ppm): δ = White solid, m.p. 166–168 °C. 1H NMR (CDCl3, 500 MHz,
3.03 (s, 3H), 3.14 (s, 3H), 7.45–7.52 (m, 3H), 7.89–7.91 (m, 2H), ppm): δ = 2.41 (s, 3H), 3.48–3.50 (t, J = 5.0 Hz, 2H), 3.68 (s, 4H),
8.15 (s, 1H). 13C NMR (CDCl3, 125 MHz, ppm): 35.4, 41.4, 3.75–3.77 (t, J = 4.8 Hz, 2H), 7.27–7.28 (d, J = 8.5 Hz, 2H),
126.2, 128.6, 131.7, 142.2, 159.1; MS calcd m/z 212.27, found 7.76–7.78 (d, J = 8.5 Hz, 2H), 8.19 (s, 1H). 13C NMR (CDCl3,
213.27 [(M + 1)]+. Anal. Calcd for C9H12N2O2S: C, 50.92; 125 MHz, ppm): 21.5, 44.1, 50.2, 65.9, 66.7, 126.5, 129.3, 139.0,
1
H, 5.70; N, 13.20; Found: C, 51.03; H, 5.75; N, 13.11.
142.7, 157.5; MS calcd m/z 268.33, found 269.33 [(M + 1)]+.
N′-(4-Chlorophenylsulfonyl)-N,N-dimethylformimidamide (3d). Anal. Calcd for C12H16N2O3S: C, 53.71; H, 6.01; N, 10.44;
White solid, m.p. 117–119 °C. 1H NMR (CDCl3, 500 MHz, Found: C, 53.62; H, 6.09; N, 10.66%.
1
ppm): δ = 3.03 (s, 3H), 3.15 (s, 3H), 7.43–7.45 (d, J = 8.5 Hz,
N-Formylbenzamide (5a). White solid, m.p. 107–109 °C. H
2H), 7.82–7.84 (d, J = 8.5 Hz, 2H), 8.13 (s, 1H). 13C NMR NMR (CDCl3, 500 MHz, ppm): δ = 7.53–7.56 (t, J = 7.8 Hz, 2H),
(CDCl3, 125 MHz, ppm): 35.8, 41.8, 128.2, 128.3, 129.0, 129.2, 7.64–7.67 (t, J = 7.3 Hz, 1H), 8.02–8.03 (d, J = 7.5 Hz, 2H),
138.4, 141.1, 159.4; MS calcd m/z 246.02, found 247.02 9.41–9.43 (d, J = 9.5 Hz, 1H), 10.32–10.34 (d, J = 6.5 Hz, 1H).
[(M + 1)]+. Anal. Calcd for C9H11ClN2O2S: C, 43.81; H, 4.49; 13C NMR (CDCl3, 125 MHz, ppm): 128.1, 129.0, 130.9, 133.9,
N, 11.35; Found: C, 43.89; H, 4.47; N, 11.28%.
165.0, 166.7; MS calcd m/z 149.15, found 150.15 [(M + 1)]+.
N,N-Dimethyl-N′-(4-nitrophenylsulfonyl)formimidamide (3e). Anal. Calcd for C8H7NO2: C, 64.42; H, 4.73; N, 9.39; Found:
White solid, m.p. 197–201 °C. 1H NMR (CDCl3, 500 MHz, C, 64.65; H, 4.75; N, 9.50%.
ppm): δ = 3.06 (s, 3H), 3.19 (s, 3H), 8.07–8.09 (d, J = 9.0 Hz,
N-Formyl-4-methylbenzamide (5b). White solid, m.p.
2H), 8.16 (s, 1H), 8.31–8.32 (d, J = 7.0 Hz, 2H). 13C NMR 130–132 °C. H NMR (CDCl3, 500 MHz, ppm) δ = 2.43 (s, 3H),
(CDCl3, 125 MHz, ppm): 35.7, 41.7, 124.0, 127.9, 148.1, 149.5, 7.32–7.33 (d, J = 8.0 Hz, 2H), 7.91–7.93 (d, J = 8.0 Hz, 2H),
159.4; MS calcd m/z 257.05, found 258.05 [(M + 1)]+. Anal. 9.38–9.40 (d, J = 9.5 Hz, 1H), 10.34 (s, 1H). 13C NMR, (CDCl3,
Calcd for C9H11N3O4S: C, 42.02; H, 4.31; N, 16.33; Found: 125 MHz, ppm): 21.6, 128.2, 128.2, 129.7, 144.9, 165.1, 166.6;
1
C, 42.25; H, 4.35; N, 16.39%.
MS calcd m/z 163.17, found 164.17 [(M + 1)]+. Anal. Calcd for
N′-(4-Methoxyphenylsulfonyl)-N,N-dimethylformimidamide C9H9NO2: C, 66.25; H, 5.56; N, 8.58; Found: C, 66.36; H, 5.59;
(3f). White solid, m.p. 133–135 °C. 1H NMR (CDCl3, 500 MHz, N, 8.69%.
ppm): δ = 3.01 (s, 3H), 3.12 (s, 3H), 3.85 (s, 3H), 6.93–6.95 (t,
4-Chloro-N-formylbenzamide (5c). White solid, m.p.
J = 7.0 Hz, 2H), 7.82–7.84 (d, J = 9.0 Hz, 2H), 8.13 (s, 1H). 13C 183–187 °C. 1H NMR (DMSO, 500 MHz, ppm): δ = 7.59–7.61
NMR (CDCl3, 125 MHz, ppm): 35.5, 41.4, 55.5, 113.8, 128.5, (m, 2H), 8.00–8.03 (m, 2H), 9.24 (s, 1H), 11.77 (s, 1H).
134.2, 158.8, 162.2; MS calcd m/z 242.07, found 243.07 [(M + 13C NMR (DMSO, 125 MHz, ppm): 129.3, 130.8, 138.9, 164.9,
1)]+. Anal. Calcd for C10H14N2O3S: C, 49.57; H, 5.82; N, 11.56; 167.1 (one of the signals was not observed); MS calcd m/z
Found: C, 49.68; H, 5.89; N, 11.69%.
Methyl 2-(N-((dimethylamino)methylene)sulfamoyl)benzoate C, 52.34; H, 3.29; N, 7.63; Found: C, 52.55; H, 3.38; N, 7.76%.
(3g). White solid, m.p. 128–129 °C. 1H NMR (CDCl3, 500 MHz,
3-Chloro-N-formylbenzamide (5d). White solid, m.p.
ppm): δ = 3.03 (s, 3H), 3.17 (s, 3H), 3.95 (s, 3H), 7.28–7.57 135–139 °C. 1H NMR (CDCl3, 500 MHz, ppm): δ = 7.48–7.51
183.59, found 184.59 [(M + 1)]+. Anal. Calcd for C8H6ClNO2:
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(t, J = 8.0 Hz, 1H), 7.62–7.64 (m, 1H), 7.87–7.89 (m, 1H),
8.01–8.02 (t, J = 1.8 Hz, 1H), 9.39–9.41 (d, J = 9.5 Hz, 1H),
10.18–10.19 (d, J = 7.5 Hz, 1H). 13C NMR (CDCl3, 125 MHz,
ppm): 125.9, 128.5, 130.3, 132.8, 133.9, 135.5, 164.7, 165.5; MS
calcd m/z 183.59, found 184.59 [(M + 1)]+. Anal. Calcd for
C8H6ClNO2: C, 52.34; H, 3.29; N, 7.63; Found: C, 52.16;
H, 3.34; N, 7.76%.
C. A. McClary and M. S. Taylor, J. Am. Chem. Soc., 2011,
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4-Fluoro-N-formylbenzamide
(5e). White
solid,
m.p.
155–156 °C. 1H NMR (CDCl3, 500 MHz, ppm): δ = 7.21–7.25
(t, J = 8.3 Hz, 2H), 8.06–8.08 (m, 2H), 9.39–9.41 (d, J = 9.5 Hz,
1H), 10.30 (s, 1H). 13C NMR (CDCl3, 125 MHz, ppm): 116.3,
116.4, 127.17, 127.2, 130.8, 130.9, 165.0, 165.2, 165.5, 167.2
(more signals were observed due to tautomerization); MS calcd
m/z 167.14, found 168.14 [(M + 1)]+. Anal. Calcd for C8H6FNO2:
C, 57.49; H, 3.62; N, 8.38; Found: C, 57.60; H, 3.69; N, 8.49%.
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2-Fluoro-N-formylbenzamide
(5f). White
solid,
m.p.
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Chem., Int. Ed., 2009, 48, 9127–9130; (e) G. S. Kumar,
C. U. Maheswari, R. A. Kumar, M. L. Kantam and
K. R. Reddy, Angew. Chem., Int. Ed., 2011, 50, 11748–11751;
(f) Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu and X. Wan,
Angew. Chem., Int. Ed., 2012, 51, 3231–3235; (g) J. Kim,
J. Choi, K. Shin and S. Chang, J. Am. Chem. Soc., 2012, 134,
2528–2531.
1
78–82 °C. H NMR (CDCl3, 500 MHz, ppm): δ = 7.20–7.24 (m,
1H), 7.34–7.37 (m, 1H), 7.62–7.66 (m, 1H), 8.11–8.14 (m, 1H),
9.15 (s, 1H), 9.38–9.40 (m, 1H). 13C NMR (CDCl3, 125 MHz,
ppm): 116.5, 116.7, 118.6, 118.6, 125.4, 125.4, 132.2, 135.9,
136.0, 160.1, 162.1, 162.5, 163.1 (more signals were observed
due to tautomerization); MS calcd m/z 167.14, found 168.14
[(M + 1)]+. Anal. Calcd for C8H6FNO2: C, 57.49; H, 3.62; N, 8.38;
Found: C, 57.31; H, 3.65; N, 8.52%.
N-Formyl-4-nitrobenzamide
(5g). Yellow
solid,
m.p.
1
162–165 °C. H NMR (DMSO, 500 MHz, ppm) δ = 8.21–8.23 (d,
J = 8.5 Hz, 2H), 8.34–8.36 (d, J = 8.5 Hz, 2H), 9.26 (s, 1H), 11.98
(s, 1H). 13C NMR (DMSO, 125 MHz, ppm): 124.2, 130.5, 137.7,
150.6, 164.8, 166.9; MS calcd m/z 194.14, found 195.14 [(M +
1)]+. Anal. Calcd for C8H6N2O4: C, 49.49; H, 3.12; N, 14.43;
Found: C, 49.60; H, 3.16; N, 14.25%.
Acknowledgements
Financial support from the National Natural Science Foun-
dation of China (21172034), the Program for New Century
9 For the computational calculation of the structures of possi-
ble intermediates and transition states, please see the ESI†
Excellent Talents in University (NCET-11–0611), the Depart- 10 For a recent paper on asymmetric hydrogen bonding
ment of Science and Technology of Jilin Province (201215002),
the Fundamental Research Funds for the Central Universities
(11SSXT129) and the Open Project of State Key Laboratory of
system, see: A. L. Lieblein, M. Krämer, A. Dreuw, B. Fürtig
and H. Schwalbe, Angew. Chem., Int. Ed., 2012, 51, 4067–
4070.
Supramolecular Structure and Materials (SKLSSM2013006), 11 For selected examples of ion pairs involved in the reaction,
is gratefully acknowledged.
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see: ref. 7c.
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16 The efficiency of the formation of amidines and N-formy-
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cannot drive the reaction to completion. Also see the
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Org. Biomol. Chem.
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