First TDAE-mediated double addition of nitrobenzylic anions to aromatic dialdehydes

Article abstract of DOI:10.1055/S-0029-1218590

We report herein the first tetrakis(dimethylaminoEthylene (TDAE)-mediated double addition of nitrobenzylic anions to aromatic dialdehydes such as terephthalaldehyde and isophthalaldehyde, and have developed a new methodology that allows us to observe the double addition. This TDAE-mediated approach is an original and mild method with which to generate tri-aromatic diols. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1218590

844
PAPER
First TDAE-Mediated Double Addition of Nitrobenzylic Anions to Aromatic
Dialdehydes
Double
Additio
h
of
N
itrobe
n
i
zylic
A
e
nions to
A
r
romatic
r
D
ialdehy
y
de
s
Juspin, Gamal Giuglio-Tonolo, Thierry Terme, Patrice Vanelle*
Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, Universités d’Aix-Marseille I, II et III – CNRS, UMR 6264,
Laboratoire Chimie Provence, 27 Boulevard J. Moulin, 13385 Marseille Cedex 05, France
Fax +33(4)91794677; E-mail: patrice.vanelle@pharmacie.univ-mrs.fr
Received 19 October 2009; revised 28 October 2009
TDAE, an organic reducing agent, is able to react with ha-
Abstract: We report herein the first tetrakis(dimethylamino)ethyl-
logenated derivatives to generate an anion, under mild
ene (TDAE)-mediated double addition of nitrobenzylic anions to
conditions, via two sequential transfers of one elec-
aromatic dialdehydes such as terephthalaldehyde and isophthalalde-
tron.10,11 According to this strategy, we have recently de-
hyde, and have developed a new methodology that allows us to ob-
serve the double addition. This TDAE-mediated approach is an veloped several useful reactions between nitrobenzylic
original and mild method with which to generate tri-aromatic diols.
substrates and various electrophiles such as aldehydes,
ketones, a-keto esters, a-ketolactams, ketomalonates and
diketone derivatives that led to the corresponding alcohol
adducts.12 In our research program directed toward the de-
velopment of original synthetic methodologies using
TDAE, the introduction of the double reactivity concept
has been considered. We report herein the reaction be-
tween nitrobenzyl chloride derivatives and dialdehydes
such as terephthalaldehyde (2) and isophthalaldehyde (5).
Key words: TDAE, dialdehydes, reduction, nucleophilic addition,
nitrobenzyl anions
Since tetrakis(dimethylamino)ethylene (TDAE) was first
discovered by Pruett1 in 1950 (Figure 1), a large number
of applications have been developed that use this powerful
electron donor. In 1966, Carpenter2 showed that TDAE
can be used as a single electron transfer (SET) reagent in
dehalogenation processes using CF3CCl2CCl3 and
CF3CCl2CCl2CF3 as substrates. Pawelke3 later found that
at low temperatures, TDAE and CF3I form a charge-trans-
fer complex that can act as a nucleophilic trifluorometh-
ylating reagent in polar solvents. In 1998,4 Médebielle
showed that TDAE could generate stable anions derived
from bromodifluoromethylated heterocycles. Later, in
19995 it was demonstrated that the CF3I/TDAE reagent
combination could promote nucleophilic trifluoromethy-
lation of p-toluenesulfinimides with very good diastereo-
selectivities. Nishiyama confirmed that TDAE could be
used in the reductive debromination of 1,2-bis(bromoeth-
yl)arene and in the reductive dimerization of a-bromo-
esters.6 Moreover, Tanaka7,8 has discovered that TDAE
could be used in several metal-mediated coupling reac-
tions. Since 2005, Murphy and collaborators9 focused
their research on TDAE-analogs as super-electron-do-
nors, and a range of tetraazaalkenes have be used to re-
duce sulfones, sulfonamides and enhanced iodoaryl
compounds in order to generate indolines, bicyclic lac-
tones and tetrahydrofurans.
In order to explore this original reactivity, a first attempt
was carried on with two equivalents of p-nitrobenzyl chlo-
ride (1) and one equivalent of dialdehyde 2 (Scheme 1).
Unfortunately, we observed the formation of dimer 3
(4,4¢-dinitrobibenzyl) in 90% yield.12a To reduce the ex-
tent of dimer formation, the reaction was then performed
with one equivalent of chloride 1 and three equivalents of
the dialdehyde 2, with the TDAE added slowly to the mix-
ture at –20 °C. However, only 51% of the desired aldol 4a
was isolated and no trace of the double addition adduct
was been observed.
NO2
Cl
CHO
3
O2N
TDAE, DMF, N2
CHO
+
+
–20 °C, 1 h; r.t., 2 h
CHO
NO2
OH
4a
1
2
3
4a
O2N
2 equiv 1 equiv
90% 0%
1 equiv 3 equiv
5% 51%
Me
N
Me
N
Scheme 1 Preliminary study
Me
Me
Me
Me
When chloride 1 is added slowly at –20 °C to a mixture of
sodium iodide, dialdehyde 2 and TDAE in anhydrous
DMF, the double addition product 4b was obtained in
33% yield (Table 1, entry 1). The sodium iodide salt must
facilitate the reaction by halogen-exchange activation.13
In order to optimize the synthesis of derivative 4b, we
N
N
Me
Me
Figure 1 Tetrakis(dimethylamino)ethylene (TDAE)
SYNTHESIS 2010, No. 5, pp 0844–0848
Advanced online publication: 07.12.2009
x
x
.
x
x
.2
0
1
0
DOI: 10.1055/s-0029-1218590; Art ID: Z22109SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Double Addition of Nitrobenzylic Anions to Aromatic Dialdehydes
845
Table 1 Influence of Experimental Conditions on the Reaction of Chloride 1 and Dialdehyde 2a
Entry
1 (equiv)
2.0
TDAE (equiv)
Time (h)
Yield of 4a (%)b Yield of 4b (%)b Global yield (%)b
1
2
3
4
5
6
7
8
3.0
2.4
3.5
4.5
3.0
3.0
3.5
3.5
2
2
15
5
33
33
49
44
33
33
58
29
48
38
54
63
95
87
65
44
2.2
3.0
2
5
4.0
2
19
62
54
7
2.0
24
48
24
48
2.0
3.0
3.0
15
a Reagents and conditions: 1 was added to a mixture of NaI (0.4 equiv), 2 (1 equiv) and TDAE, N2, at –20 °C for 1 h then at r.t. for 24 h.
b Yield refers to chromatographically isolated pure products and are relative to dialdehyde 2.
Cl
timized conditions for the TDAE-initiated reaction of
p-nitrobenzyl chloride (1) with isophthalaldehyde (5;
Scheme 3); under these conditions the derivative 6b, cor-
responding to the double addition, was isolated with an
excellent yield (82%). When the TDAE-initiated reactivi-
ty of o-nitrobenzyl chloride derivatives 7 and 8 toward
terephthalaldehyde (2) and isophthalaldehyde (5) was in-
vestigated, we found that these conditions furnished a cor-
responding mixture of aldols 9a–12a and diols 9b–12b
(Scheme 4, Table 2).
CHO
OH
4a
O2N
NO2
1
TDAE, NaI, DMF, N2
–20 °C, 1 h
NO2
+
+
OH
CHO
As for the p-nitrobenzyl chloride series, we could gener-
ate the diol derivatives under these new conditions (1
equiv of dialdehyde, 3 equiv of chloride, 3.5 equiv of
TDAE). These results confirmed that this method could
be extended to different chlorides and aromatic dialde-
hydes.
OH
O2N
4b
CHO
2
Scheme 2 TDAE-initiated reactivity of p-nitrobenzyl chloride (1)
and terephthalaldehyde (2)
Cl
CHO
In conclusion, this study presents the first TDAE-mediat-
ed double addition of nitrobenzylic anions to aromatic di-
aldehydes. We have developed a new protocol by
changing the order of addition of the reagents. This origi-
nal process allows us to generate tri-aromatic diols that
could be used as starting materials for dehydration and
electrocyclization reactions in order to obtain polycyclic
conjugated molecules. The synthesis of dissymetric diols
via a ‘one-pot’ procedure is under investigation.
OH
6a 5%
NO2
1
+
O2N
TDAE, NaI, DMF, N2
–20 °C, 1 h; r.t., 24 h
+
HO
CHO
NO2
CHO
Melting points were determined on a Buchi capillary melting point
apparatus and are uncorrected. Elemental analyses were performed
by the Centre de Microanalyses of the spectropole (Aix-Marseille
5
OH
O2N
6b 82%
1
University). Both H and 13C NMR spectra were determined on a
Scheme 3 TDAE-initiated reactivity of p-nitrobenzyl chloride 1
and isophthalaldehyde 5
Brucker AC 200 spectrometer. The 1H NMR chemical shifts (d) are
reported as parts per million downfield from tetramethylsilane
(TMS), and the 13C NMR chemical shifts were referenced to the sol-
vents peaks: CDCl3 (d = 76.9 ppm) or DMSO-d6 (d = 39.6 ppm).
Absorptions are reported with the following notations: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet or overlapping). The
following adsorbents were used for column chromatography: silica
gel 60 (Merck, particle size 0.063–0.200 mm, 70–230 mesh
ASTM). TLC were performed on 5 × 10 cm aluminum plates coat-
ed with silica gel 60 F-254 (Merck) in an appropriate solvent sys-
tem.
studied the influence of the chloride/dialdehyde/TDAE
ratio and reaction time (Table 1). The best reaction condi-
tions for the synthesis of compound 4b were found to be:
3.5 equivalents of TDAE, 3.0 equivalents of 1 and 0.4
equivalents of sodium iodide at –20 °C for one hour fol-
lowed by 24 hours at room temperature under an inert at-
mosphere (Scheme 2; Table 1, entry 7). In order to extend
and validate this new methodology, we applied these op-
Synthesis 2010, No. 5, 844–848 © Thieme Stuttgart · New York

846
T. Juspin et al.
PAPER
R1
R2
OH
CHO
NO2
CHO
NO2
R1
R2
TDAE, NaI, DMF, N2
–20 °C, 1 h; r.t., 24 h
Cl
+
NO2
+
OH
R2
NO2
OH
R2
R1
CHO
9a, 10a
9b, 10b
R1
2
NO2
CHO
HO
CHO
NO2
R1
R2
TDAE, NaI, DMF, N2
–20 °C, 1 h; r.t., 24 h
Cl
+
NO2
R2
+
R1
NO2
CHO
OH
R2
OH
R2
R1
7 R1 = H, R2 = H
5
11a, 12a
11b, 12b
8 R1 = 5-Me, R2 = H
R1
Scheme 4 Extension of the TDAE-initiated reactivity with dialdehyde 2 and 5
Table 2 Reaction of Dialdehydes 2 and 5 with Chlorides 7 and 8 using TDAE
Entry
Chloride R1
R2
H
H
H
H
Dialdehyde Mono addition yield (%)a Double addition yield (%)a Global yield (%)a
1
2
3
4
7
8
7
8
H
2
2
5
5
32 (9a)
28 (10a)
7 (11a)
11 (12a)
43 (9b)
75
96
83
65
Me
H
68 (10b)
76 (11b)
54 (12b)
Me
a Yield refers to chromatographically isolated pure products and are relative to dialdehyde 2 or 5.
TDAE Reaction; General Procedure
1H NMR (200 MHz, DMSO-d6): d = 3.01 (m, 4 H, 2 × CH2), 4.80
(m, 2 H, 2 ×CH), 5.38 (d, J = 5.4 Hz, 2 H, 2 ×OH), 7.25 (s, 4 H,
ArH), 7.43 (d, J = 8.8 Hz, 4 H, ArH), 8.09 (d, J = 8.8 Hz, 4 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 45.1, 72.7, 122.8, 125.5, 130.7,
143.7, 145.8, 147.6.
In a two-necked flask equipped with a silica gel drying tube and a
nitrogen inlet under nitrogen at –20 °C, TDAE (1.04 mL, 4.47
mmol, 3.0 equiv or 1.21 mL, 5.21 mmol, 3.5 equiv) was added drop-
wise (via a syringe) to a solution of dialdehyde (0.2 g, 1.49 mmol,
1 equiv) and NaI (0.09 g, 0.60 mmol, 0.4 equiv) in anhydrous DMF
(5 mL). A solution of corresponding benzyl chloride 1, 7 or 8 (2
equiv or 3 equiv) in anhydrous DMF (2 mL) was added dropwise
over 1 h. The solution was vigorously stirred at –20 °C for 1 h and
then warmed to r.t. for 24 h. A solution of aq HCl (0.1 N, 100 mL)
was slowly added in order to quench the reaction, then the aqueous
solution was extracted with CH2Cl2 (3 × 50 mL), and the combined
organic layers were washed with H2O (3 × 100 mL), dried over
MgSO4 and the solvent removed under reduce pressure. Purification
of the crude product by gradient chromatography (CH2Cl2–EtOAc,
1:0→2:1) gave the corresponding aldols (4a, 6a, 9a, 10a, 11a, and
12a) and diols (4b, 6b, 9b, 10b, 11b, and 12b).
Anal. Calcd for C22H20N2O6: C, 64.70; H, 4.94; N, 6.86. Found: C,
64.37; H, 4.15; N, 6.67.
3-[1-Hydroxy-2-(4-nitrophenyl)ethyl]benzaldehyde (6a)
Yellow solid; mp 131 °C.
1H NMR (200 MHz, CDCl3): d = 1.86 (br s, 1 H, OH), 3.15 (d,
J = 6.5 Hz, 2 H, CH2), 5.06 (t, J = 6.5 Hz, 1 H, CH), 7.34 (d, J = 8.7
Hz, 2 H, ArH), 7.49–7.61 (m, 2 H, ArH), 7.80–7.88 (m, 2 H, ArH),
8.15 (d, J = 8.7 Hz, 2 H, ArH), 10.02 (s, 1 H, CHO).
13C NMR (50 MHz, CDCl3): d = 45.5, 74.2, 123.6, 126.5, 129.3,
129.6, 130.4, 131.9, 136.6, 144.4, 145.3, 146.9, 192.0.
Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C,
66.16; H, 4.93; N, 5.39.
4-[1-Hydroxy-2-(4-nitrophenyl)ethyl]benzaldehyde (4a)
Orange solid; mp 131 °C.
1H NMR (200 MHz, CDCl3): d = 3.14 (d, J = 6.4 Hz, 2 H, CH2),
5.05 (t, J = 6.4 Hz, 1 H, CH), 7.31 (d, J = 8.8 Hz, 2 H, Ar-H), 7.47
(d, J = 8.2 Hz, 2 H, Ar-H), 7.84 (d, J = 8.2 Hz, 2 H, Ar-H), 8.12 (d,
J = 8.8 Hz, 2 H, Ar-H), 9.98 (s, 1 H, CHO).
13C NMR (50 MHz, CDCl3): d = 45.3, 74.3, 123.5, 126.4, 130.0,
130.4, 136.0, 145.2, 146.9, 150.0, 191.8.
1,1¢-(1,3-Phenylene)bis[2-(4-nitrophenyl)ethanol] (6b)
Yellow solid; mp 132 °C.
1H NMR (200 MHz, DMSO-d6): d = 2.98 (d, J = 6.5 Hz, 4 H, 2 ×
CH2), 4.82 (m, 2 H, 2 × CH), 5.42 (d, J = 4.6 Hz, 2 H, 2 × OH), 7.21
(m, 3 H, ArH), 7.33 (s, 1 H, ArH), 7.44 (d, J = 8.4 Hz, 4 H, ArH),
8.12 (d, J = 8.4 Hz, 4 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 45.4, 73.1, 123.0, 123.6, 124.6,
127.7, 130.9, 145.0, 146.1, 147.8.
Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C,
66.32; H, 4.86; N, 5.78.
Anal. Calcd for C22H20N2O6: C, 64.70; H, 4.94; N, 6.86. Found: C,
64.58; H, 5.21; N, 6.89.
1,1¢-(1,4-Phenylene)bis[2-(4-nitrophenyl)ethanol] (4b)
Yellow solid; mp 222 °C.
Synthesis 2010, No. 5, 844–848 © Thieme Stuttgart · New York

PAPER
Double Addition of Nitrobenzylic Anions to Aromatic Dialdehydes
847
4-[1-Hydroxy-2-(2-nitrophenyl)ethyl]benzaldehyde (9a)
Brown solid; mp 103 °C.
1,1¢-(1,3-Phenylene)bis[2-(2-nitrophenyl)ethanol] (11b)
Brown oil.
1H NMR (200 MHz, DMSO-d6): d = 2.26 (br s, 1 H, OH), 3.17 (dd,
J = 8.8, 13.6 Hz, 1 H, CH2), 3.42 (dd, J = 8.8, 13.6 Hz, 1 H, CH2),
5.16 (dd, J = 3.8, 8.8 Hz, 1 H, CH), 7.29–7.54 (m, 3 H, ArH), 7.58
(d, J = 8.1 Hz, 2 H, ArH), 7.88 (d, J = 8.1 Hz, 2 H, ArH), 7.96–8.00
(m, 1 H, ArH), 10.01 (s, 1 H, CHO).
13C NMR (50 MHz, DMSO-d6): d = 41.5, 72.4, 124.3, 126.5, 127.9,
129.6, 132.8, 132.9, 133.5, 135.4, 143.4, 150.2, 152.3, 192.9.
1H NMR (200 MHz, CDCl3): d = 2.88 (br s, 2 H, 2 × OH), 3.05–3.28
(m, 4 H, 2 × CH2), 4.82–4.89 (m, 2 H, 2 × CH), 7.18–7.48 (m, 10 H,
ArH), 7.84 (d, J = 7.8 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 42.3, 73.8, 124.4, 124.9, 127.4,
128.4, 132.6, 133.1, 133.4, 143.8, 149.5.
Anal. Calcd for C22H20N2O6: C, 64.70; H, 4.94; N, 6.86. Found:
64.46; H, 5.31; N, 6.78.
Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C,
66.38; H, 4.89; N, 5.25.
3-[1-Hydroxy-2-(5-methyl-2-nitrophenyl)ethyl]benzaldehyde
(12a)
1,1¢-(1,4-Phenylene)bis[2-(2-nitrophenyl)ethanol] (9b)
Brown solid; mp 105.5 °C.
Orange solid; mp 219 °C.
1H NMR (200 MHz, CDCl3): d = 2.39 (s, 3 H, CH3), 3.13 (dd,
J = 9.1, 13.4 Hz, 1 H, CH2), 3.43 (dd, J = 3.7, 13.4 Hz, 1 H, CH2),
5.14 (dd, J = 3.7, 9.1 Hz, 1 H, CH), 7.13 (s, 1 H, ArH), 7.20 (d,
J = 8.4 Hz, 1 H, ArH), 7.53 (t, J = 7.6 Hz, 1 H, ArH), 7.71 (d,
J = 7.6 Hz, 1 H, ArH), 7.81 (d, J = 7.6 Hz, 1 H, ArH), 7.92 (d,
J = 8.4 Hz, 1 H, ArH), 7.94 (s, 1 H, ArH), 10.02 (s, 1 H, CHO).
13C NMR (50 MHz, CDCl3): d = 21.3, 43.3, 73.6, 125.3, 126.9,
128.6, 128.9, 129.2, 131.8, 133.1, 134.2, 136.6, 144.3, 145.1, 147.3,
192.2.
1H NMR (200 MHz, DMSO-d6): d = 3.15 (d, J = 6.4 Hz, 4 H, 2 ×
CH2), 4.72 (m, 2 H, 2 × CH), 5.38 (d, J = 4.7 Hz, 2 H, 2 × OH), 7.26
(s, 4 H, ArH), 7.43–7.50 (m, 4 H, ArH), 7.57–7.64 (m, 2 H, ArH),
7.89 (d, J = 7.5 Hz, 2 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 42.0, 72.5, 124.2, 125.5, 127.7,
132.7, 133.4, 144.3, 150.2.
Anal. Calcd for C22H20N2O6: C, 64.70; H, 4.94; N, 6.86. Found: C,
64.74; H, 5.17; N, 6.72.
Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C,
67.44; H, 5.64; N, 4.77.
4-[1-Hydroxy-2-(5-methyl-2-nitrophenyl)ethyl]benzaldehyde
(10a)
Brown solid; mp 126 °C.
1,1¢-(1,3-Phenylene)bis[2-(5-methyl-2-nitrophenyl)ethanol]
(12b)
1H NMR (200 MHz, CDCl3): d = 2.40 (s, 3 H, CH3), 3.10 (dd,
J = 9.0, 13.5 Hz, 1 H, CH2), 3.43 (dd, J = 3.6, 13.5 Hz, 1 H, CH2),
5.14 (dd, J = 3.6, 9.0 Hz, 1 H, CH), 7.12 (s, 1 H, ArH), 7.21 (d,
J = 8.4 Hz, 1 H, ArH), 7.60 (d, J = 8.2 Hz, 2 H, ArH), 7.88 (d,
J = 8.2 Hz, 2 H, ArH), 7.92 (d, J = 8.4 Hz, 1 H, ArH), 10.01 (s, 1 H,
CHO).
Brown oil.
1H NMR (200 MHz, CDCl3): d = 2.37 (s, 6 H, 2 × CH3), 2.66 (br s,
2 H, 2 × OH), 2.89–3.37 (m, 4 H, 2 × CH2), 4.95 (dd, J = 3.9, 8.8
Hz, 2 H, 2 × CH), 7.13–7.16 (m, 4 H, ArH), 7.29 (m, 3 H, ArH),
7.36 (m, 1 H, ArH), 7.82–7.86 (m, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.4, 43.2, 73.7, 125.3, 126.2,
128.6, 130.0, 133.0, 134.2, 135.8, 144.3, 147.3, 150.7, 191.9.
13C NMR (50 MHz, CDCl3): d = 38.5, 42.9, 74.1, 122.7, 124.9,
128.1, 128.5, 133.6, 134.1, 143.9, 144.2, 147.3.
Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C,
67.16; H, 5.45; N, 4.91.
Anal. Calcd for C24H24N2O6: C, 66.04; H, 5.54; N, 6.42. Found: C,
66.57; H, 5.98; N, 6.15.
1,1¢-(1,4-Phenylene)bis[2-(5-methyl-2-nitrophenyl)ethanol]
(10b)
Acknowledgment
Beige solid; mp 193 °C.
This work was supported by the Centre National de la Recherche
Scientifique. We express our thanks to V. Remusat for recording the
1H and 13C NMR spectra. T.J. thanks the Ministère de l’Enseigne-
ment Supérieur et de la Recherche for a Ph.D. grant.
1H NMR (200 MHz, CDCl3): d = 1.88 (br s, 2 H, 2 × OH), 2.41 (s,
6 H, 2 × CH3), 3.16 (dd, J = 9.1, 13.5 Hz, 2 H, CH2), 3.40 (dd,
J = 3.6, 13.5 Hz, 2 H, CH2), 5.04 (dd, J = 3.6, 9.1 Hz, 2 H, 2 × CH),
7.17 (s, 2 H, ArH), 7.19 (d, J = 8.0 Hz, 2 H, ArH), 7.43 (s, 4 H,
ArH), 7.91 (d, J = 8.0 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.0, 42.4, 72.6, 124.5, 125.5,
128.1, 133.9, 134.0, 143.4, 144.5, 147.8.
References
(1) Pruett, R. L.; Barr, J. T.; Rapp, K. E.; Bahner, C. T.; Gibson,
J. D.; Lafferty, R. H. Jr. J. Am. Chem. Soc. 1950, 72, 3646.
(2) Carpenter, W. J. Org. Chem. 1966, 31, 789.
(3) (a) Pawelke, G. J. Fluorine Chem. 1989, 42, 429.
(b) Pawelke, G. J. Fluorine Chem. 1991, 52, 229.
(4) Burkholder, C.; Dolbier, W. R. Jr.; Médebielle, M. J. Org.
Chem. 1998, 63, 5385.
(5) Xu, W.; Dolbier, R. W. Jr. J. Org. Chem. 2005, 70, 4741.
(6) (a) Nishiyama, Y.; Kabawata, H.; Kobayashi, A.; Nishino,
T.; Sonida, N. Tetrahedron Lett. 2005, 46, 867.
(b) Nishiyama, Y.; Kawabata, H. Tetrahedron Lett. 2006,
47, 5565.
Anal. Calcd for C24H24N2O6: C, 66.04; H, 5.54; N, 6.42. Found: C,
65.74; H, 5.67; N, 6.46.
3-[1-Hydroxy-2-(2-nitrophenyl)ethyl]benzaldehyde (11a)
Brown solid; mp 97.5 °C.
1H NMR (200 MHz, CDCl3): d = 2.22 (br s, 1 H, OH), 3.19 (dd,
J = 8.9, 13.6 Hz, 1 H, CH2), 3.42 (dd, J = 3.8, 13.6 Hz, 1 H, CH2),
5.15 (dd, J = 3.8, 8.9 Hz, 1 H, CH), 7.31–7.57 (m, 4 H, ArH), 7.67–
7.71 (m, 1 H, CH), 7.79–7.84 (m, 1 H, CH), 7.92–8.00 (m, 2 H,
ArH), 10.02 (s, 1 H, CHO).
13C NMR (50 MHz, CDCl3): d = 42.9, 73.4, 124.8, 126.9, 127.9,
128.9, 129.2, 131.8, 132.8, 133.6, 136.5, 145.1, 149.7, 165.1, 192.2.
(7) Kuroboshi, M.; Tanaka, M.; Kishimoto, S.; Goto, K.;
Mochisuki, M.; Tanaka, H. Tetrahedron Lett. 2000, 41, 81.
Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C,
66.35; H, 4.97; N, 5.32.
Synthesis 2010, No. 5, 844–848 © Thieme Stuttgart · New York

848
T. Juspin et al.
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Synthesis 2010, No. 5, 844–848 © Thieme Stuttgart · New York