A general and convenient method for the synthesis of 2,4-dinitrobenzyl ketones. Almost unlimited access to 2-substituted 6-nitroindoles from 2,4-dinitrotoluene and aldehydes

Article abstract of DOI:10.1039/c7nj04919f

2,4-Dinitrotoluene reacts in the presence of catalytic amounts of DBU with aldehydes to form the corresponding alcohols in good yields (usually above 65%). The obtained alcohols can be readily oxidized to 2,4-dinitrobenzyl ketones, which were used for the synthesis of 6-nitroindoles with various substituents in the 2-position. Starting from non-racemic aldehydes, non-racemic 2-substituted 6-nitroindoles were obtained.

Full text of DOI:10.1039/c7nj04919f

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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DOI: 10.1039/C7NJ04919F
Journal Name
ARTICLE
General and convenient method of the synthesis of 2,4-
dinitrobenzyl ketones. Almost unlimited access to 2-substituted
6-nitroindoles from 2,4-dinitrotoluene and aldehydes.
Received 00th January 20xx,
Accepted 00th January 20xx
Robert Bujok,*a Marcin Wiszniewski,b Piotr Cmocha and Zbigniew Wróbela
DOI: 10.1039/x0xx00000x
2,4-Dinitrotoluene reacts in the presence of catalytic amounts of DBU with aldehydes to form corresponding alcohols
in good yields (usually above 65 %). Obtained alcohols can be readily oxidized to 2,4-dinitrobenzyl ketones, which were
used for the synthesis of 6-nitroindoles with various substituents in the 2-position. Starting from non-racemic aldehydes,
non-racemic 2-substituted 6-nitroindoles were obtained.
www.rsc.org/
moderate yields (20 – 60 %; usually ca. 40 %) in the reaction of
m-nitroaniline with enolizable ketones in the presence of
t-BuOK as base (Figure 2, path d). 2-Substituted 6-nitro-indoles
also were formed in this method, but the yields did not exceed
Introduction
Indoles are one of the most important structural motif found in
many biologically-active compounds and natural products such as
aplicyanins,1a phytoalexin,1b panicullidine B1b and stephacidin B.1c
Also 6-nitroindoles exhibit biological activity, for example
cytotoxity,1d antibacterial activity1e (staphylococus aureus,
pseudomonas aeruginosa) and antifungal activity.1f Representative
structures are shown on the Figure 1. Due to the broad application
of indoles, synthesis of these compounds is still of substantial
interest.2
20 %.
A
few years ago we described transition-metal-free
method of the synthesis of 2-substituted 6-nitroindoles8 from
m-dinitrobenzene and chloromethyl ketones via 2,4-
dinitrobenzyl ketones (Figure 2, path e).
H2N
S
H
N
O
N
N
O
N
H
OCH3
N
O2N
N
N
O2N
O2N
NH2
General methods for the synthesis of 2-substitued indoles
consist of palladium-catalyzed direct arylation of indoles3
(Figure 2, path a) and addition of nitrogen nucleophiles to
alkynes (Figure 2, path b)4 including one-pot amination /
intramolecular cyclization (Figure 2, path c).5 Yields of products
are usually good, but following this strategy mostly aryl
substituents were introduced into indole ring. It should be
stressed that alkynes used in cyclization step are obtained
from rather expensive iodoarenes. Moreover, both steps
(Sonogashira reaction followed by cyclization of arylalkynes to
indoles) require expensive transition metal catalysts, what can
be a problem if the synthesis is carried-out in large scale.
H
H
H
CYTOTOXIC ACTIVITY
ANTIFUNGAL ACTIVITY
ANTIBACTERIAL ACTIVITY
Figure 1 Selected examples of biologically-active 6-nitro-2-
substituted indoles.
NO2
O
Cl
+
R
N
NO2
H
e
a
NO2
R
Ar
O
b
NO2
Ar
N
H
SnCl2
NH-PG
Ar = aryl
R
c
N
OH
O2N
It should be stressed that transition metal catalysts often
require arduous removal, particularly if the product has
potential pharmaceutical applications.6
Ar
R
Ar
N
O2N
H
2-substitituted 4-nitroindoles were synthesized7 in
NH2
R=aryl, alkil
X
NO2
R'
NO2
R'
d
a.Institute of Organic Chemistry Polish Academy of Sciences, ul. Kasprzaka 44/52,
01-224 Warsaw, Poland, e-mail: robert.bujok@icho.edu.pl; b Faculty of Chemistry
Warsaw University of Technology, ul. Noakowskiego 3, 00-664 Warsaw.
O
R
R
+
+
R
R`
N
N
O2N
NH2
H
H
< 20 %
R=aryl, alkil
Electronic Supplementary Information (ESI) available:
Figure 2 Synthetic strategies towards 2-substituted indoles.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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ARTICLE
This method is of general character. It allows to introduce
various substituents (aryl, alkyl) in the 2-position, but it is
limited by the availability of chlorometylketones, which are
substrates for the key-intermediates, namely, 2,4-
dinitrobenzylketones.
Journal Name
NO2
S
N
O
O
View Article Online
DOI: 10.1039/C7NJ04919F
SH
+
a
Br
R
R
R
+
NO2
NBu4F / UV irradiation
b
S
N
S
O
NO2
F
NO2
NO2
c
O
S
R
NO2
R
SO2
+
R
OEt
N
S
N
O
O
Chloromethyl ketones are rather rarely available compounds –
only few (R=Me, t-Bu, Ph), are commercially available, so it is
worthy to consider other methods of the synthesis of 2,4-
dintrobenzylketones.
SO2
NO2
-
NO2
only for R= CF3, COOEt
d
NO2
O
Cl
+
R
NO2
Jorgensen9a et al. obtained discussed ketones starting from 2-
mercaptobezothiazol
and
bromoacetophenones
bearing
Figure 3 Synthetic strategies towards 2,4-dinitro-benzylketones.
substituents in phenyl ring (Figure 3, path a). This method however
requires 3 steps and suffers from low atom economy (benzothiazol
group is introduced in first step and removed in last one).
OH
O
R
R
Cervera and Marquet9b described synthesis of 2,4-
dinitrobenzylketones in the photoreaction of m-dinitrobenzene
with methylketones in the presence of NBu4F under UV irraditiation
(Figure 3, path b). This method is limited to methyl alkyl ketones
only.
NO2
R-CHO
NO2
NO2
[O]
SnCl2
8
BrCH2Bz
Et3N
R
R
N
OH
O2N
N
O2N
H
NO2
2
NO2
3
NO2
4
5
NEW METHOD OF THE SYNTHESIS OF
2,4-DINITROBENZYL KETONES
THIS WORK
As we mentioned, we synthesized the key-intermediates in the
reaction of m-dinitrobenzene with chloromethyl ketones8 (Figure 3,
path d) and also in the reaction of 2,4-dinitrotoluene with ethyl
trifluoroacetate or diethyl oxalate (Figure 3, path c).8 It is
noteworthy that esters of simple aliphatic acids (ethyl acetate), as
well, esters of aromatic acids (methyl 1-naphthoate) are inactive
under these conditions. Apparently only in the presence of a strong
electron withdrawing group (CF3, COOEt) connected with carbonyl
group, the last one is electrophilic enough to undergo reaction with
carbanion of 2,4-dinitrotoluene which is a very weak nucleophile.
Figure 4 Concept of the new general method of the synthesis of
2,4-dinitrobenzyl ketones (3) and using of the latter in synthesis of
N-hydroxy-2-substituted 6-nitroindoles (4) by previously described
method.
Table 1 Effect of amount of DBU and amount of the aldehyde 1a on
the yield of the product 2a (isolated yields are given).
OH
CHO
O2N
DBU
O2N
N
+
DMF, temp.
Reassuming, there is no general way to synthesize 2,4-
dinitrobenzylketones which are interesting substrates in organic
synthesis. Thus a novel methodologies are still desired.
N
NO2
1a
NO2
2a
Results and discussion
Entry
1a
(eq.)
4.5
3.0
3.0
DBU
(eq.)
2.5
0.50
0.10
0.10
Temp.
*°C+
-30
-30
-20
t
[h]
2
3
24
48
Yield of
2a
34
32
45
In this paper we present a convenient method of the synthesis
of 2,4-dinitrobenzyl ketones (3) from 2,4-dinitrotoluene and various
aldehydes via corresponding alcohols (2) (Figure 4). Aldehydes are
cheap, commercially available and highly active electrophiles. With
new general method of the synthesis of the key-intermediates (3) in
hands, we were able to introduce various substituents into the 2-
position of indole (including non-racemic groups) using previously
described8 reaction of ketones (3) with SnCl2 and expand it to broad
range of new derivatives. It should be stressed that N-hydroxy-2-
substituted 6-nitroindoles (4) can be transformed into 2-substituted
6-nitroindoles (5) in excellent yields8 (usually above 90 %).
Keeping in mind that the key-intermediates (3) bearing simple
substituents (R=Me, Ph) can be synthesized from m-dinitrobenzene
and respective chloromethyl ketones, we focused on more complex
cases and we used pyridine-3-carbaldehyde (1a) as a model
aldehyde.
1
2
3
4
1.5
-20
72
O
CHO
CH2-
catalytic amount of DBU
-DBU * H+
O2N
O2N
N
O2N
OH
N
NO2
NO2
NO2
O
CH2-
O2N
O2N
O2N
O2N
+
N
N
+
NO2
NO2
NO2
NO2
Scheme 1 Concept of using of catalytic amount of DBU.
2 | J. Name., 2012, 00, 1-3
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ARTICLE
NO2
In the initial experiment (Table 1, entry 1) we used 2.5
equivalents of DBU, 4.5 equivalents of the aldehyde (1a) and we
performed the reaction in DMF at -30°C. The reaction was
completed in 2 hours, but large amount of by-products was formed
and desired product (2a) was obtained in moderate yield (34 %).
View Article Online
DOI: 10.1039/C7NJ04919F
O2N
HO
O
CHO
O2N
0.10 eq.DBU
+
+
DMF, -20 °C, 3d.
NO2
CHO
1n
HO
HO
NO2
NO2
Because alkoxide anion formed in the reaction of a carboanion
of 2,4-dinitrotoluene with the aldehyde (1a) can act also as a base
and deprotonate 2,4-dinitrotoluene (Scheme 1), we used 0.5
equivalent of DBU (table 1, entry 2).
O2N
O2N
4 mmol
8 mmol
2n', 35 %
2 mmol
2n, 49 %
33 %
58 %
Scheme 2 Reaction of 2,4-dinitrotoluene with terephthalaldehyde
1n (isolated yields are given).
The reaction was slightly slower (it was completed in 3 hours),
but still product was formed in moderate yield (32 %) because of
formation of large amounts of unidentified by-products. In the
presence of 0.10 equivalent of DBU (entry 3), the reaction was very
Aliphatic aldehydes react slower than aromatic ones −moderate
slow at -30 °C and after 3 hours we continued it overnight at -20 °C. conversions were observed under optimized conditions for 1a, but
when four equivalents of the substrates (1f, 1i-1k, 1m) and 0.25
equivalent of DBU were used, the expected products were obtained
in yields above 60 % (usually ca. 75 %) after 2 days at -20 °C.
The yield increased to 45 %.
Finally, when we used 1.5 equivalent of pyridine-3-
carbaldehyde (1a) and 0.10 equivalent of DBU small amount of 2,4-
dinitrotoluene was still present after 48 hours at -20 °C, but the
reaction undergone selectively and the product was isolated in
quite good yield (72 %). We have found this result satisfactory and
applied these conditions to screen the scope of the reaction (Table
2).
In the case of rather precious non-racemic aldehydes 1g, 1h, 1l
we used 1.5 equivalent of these substrates, 0.25 equivalent of DBU
and satisfactory results were obtained (50 – 68 %) after 3 days at
-20°C. It should be mentioned, that in the reaction of the aldehyde
1l with 2,4-dinitrotoluene used in excess (1.5 equivalent) much
worse result was obtained – product 2l was isolated in 15 % yield.
This method is of general character – aliphatic, carbocyclic,
aromatic and heteroaromatic aldehydes react with 2,4-
dinitrotoluene in the presence of catalytic amounts of DBU giving
desired 2,4-dinitrobenzyl alcohols (2) in good yields (50 – 78 %;
usually above 65 %).
We also carried-out the reaction of 2,4-dinitrotoluene with
terephthalaldehyde (Scheme 2). We wanted to obtain the product
of ‘bis-addition’ (2n) of 2,4-dinitrotoluene to the aldehyde 1n, but
product of ‘mono-addition’ (2n’) was also present in the reaction
mixture. When nitrocompound was used in excess, slightly better
yield of desired product (2n) was obtained (58 %), but still product
2n’ was observed and the progress of the reaction stopped.
Table 2 Synthesis of 2,4-dinitrobenzyl alcohols 2 (isolated yields are
given).
OH
R
O2N
0.10 - 0.25 eq. DBU
With the new general method of the synthesis of 2,4-
dinitrobenzyl alcohols (2) in hands, we decided to oxidize them to
corresponding dinitrobenzyl ketones (3).
R
CHO
O2N
+
DMF, -20 °C, 2-3d.
1a - 1m
NO2
NO2
OH
OH
OH
OH
In the case of alcohols lacking sensitive groups (2d – 2f, 2i − 2k,
2n) we used aqueous solution of CrO3 (Jones oxidation). It is simple
method and for robust compounds it gives good results (Table 3).
O
O2N
S
O2N
O2N
O2N
N
NO2
NO2
NO2
NO2
2d, 78 %
2c, 75 %
2b, 65 %
2a, 72 %
When R=alkyl or cycloalkyl, corresponding ketones were
obtained in almost quantitative yields. Aromatic derivatives
(R=phenyl, naphthyl) under these conditions form some tars and
therefore worse results were obtained. It is noteworthy, that in all
cases pure products were obtained after simple aqueous work-up
and no further purification was needed in this procedure.
OH
OH
OH
OH
N
Bz
O2N
O2N
N
Boc
O2N
O2N
NO2
NO2
2g, 56 %
NO2
2h, 50 %
NO2
2e, 71 %
2f, 75 %
OH
OH
OH
OH
OH
O2N
O2N
O2N
OTHP
O2N
O2N
Poor result was obtained in the case of ketone 3b (12 %) using
Jones oxidation and the more sensitive alcohols were oxidized by
Dess – Martin periodinane (Table 4). All investigated alcohols
except pyridine derivative (2a) undergo oxidation smoothly giving
corresponding ketones 3 in goods yields (usually above 80 %).
NO2
NO2
2m, 61 %
NO2
2l, 68 %
NO2
2j, 75 %
NO2
2k, 76 %
2i, 65 %
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Table 3 Jones oxidation of selected 2,4-dinitrobenzyl alcohols 2d –
2f, 2i − 2k, 2n (isolated yields are given).
and corresponding chloromethyl ketone (yields ca. 80 %), but
method described in this paper is much more general and it allows
to synthesise new derivatives.
View Article Online
DOI: 10.1039/C7NJ04919F
OH
O
R
R
CrO3, diluted H2SO4
acetone, RT, 1h
O2N
O2N
All prepared key−intermediates (3a) − (3n) were used in
synthesis of 2-substituted 6-nitroindoles (4) with using of SnCl2
according to described procedure8 and in all cases except (3g) and
(3l) desired products were isolated in satisfactory yields (usually
50 % − 60 %; Table 5). As we expected, 2-alkyl (4i, 4j, 4k), 2-
cycloalkyl (4f), 2-aryl (4d, 4e) and 2-heteroaryl (4a, 4b, 4c) indoles
can be synthesized by this methodology in similar yields. Especially
good result was obtained for naphthyl derivative (4d) (72 %).
NO2
NO2
2d - 2f, 2i - 2k, 2n
3d - 3f, 3i - 3k, 3n
O
O
O
NO2
O2N
O2N
O2N
O2N
O
NO2
NO2
NO2
3f, 97 %
We also obtained “bis-indole” (4n) in moderate yield (30 %).
Taking into account complexity of the structure, this result is still
acceptable.
3e, 68 %
3d, 61 %
O
O
O
O
NO2
O2N
O2N
O2N
In the case of ketones bearing protecting groups (3g) and (3l)
complex mixtures were formed and no products were isolated. We
supposed that inappropriate protecting groups were chosen and
the groups were removed under these reaction conditions.
O2N
3n, 73 %
NO2
NO2
NO2
3i, 93 %
3j, 96 %
3k, ~100 %
Table 5 Synthesis of N-hydroxy-2-substituted 6-nitroindoles (4)
Table 4 Oxidation of 2,4-dinitrobenzyl alcohols by Dess-Martin
from 2,4-dinitrobenzyl ketones (isolated yields are given).
periodinane (isolated yields are given).
O
O
OH
R
SnCl2
O2N
R
R
R
Dess-Martin periodinane
O2N
N
O2N
NO2
AcOEt / EtOH, RT, 1d.
CH2Cl2, 0 °C - RT, 1-1.5 h.
OH
NO2
4a - 4f, 4h - 4k, 4l - 4m
NO2
NO2
2a -2c, 2g-2h, 2l-2m
3a - 3n
3a -3c, 3g-3h, 3l-3m
NEWLY SYNTHESISED INDOLES
O
O
O
O
O
N
OH
S
NO2
N
OH
N
OH
N
NO2
NO2
N
Boc
O2N
O
O2N
S
O2N
O2N
N
4c, 60 %
4b, 54 %
4a, 50 %
NO2
3g, 83 %
NO2
3b, 81 %
(12 % in Jones oxidation)
NO2
NO2
3c, 76 %
3a, 65 %
O
O
O
N
OH
NO2
N
N
N
OH
NO2
NO2
Bz
OH
N
Bz
O2N
O2N
O2N
OTHP
4h, 41 %
4f, 60 %
4d, 72 %
NO2
3h, 88 %
NO2
NO2
3l, 91 %
3m, 80 %
N
OH
NO2
N
OH
NO2
N
OH
NO2
In the case of alcohol 2a, relatively large amount of by-products
4j, 58
4m, 46 %
4k, 50 %
was formed. Moreover, purification of the product 3a was
troublesome which affected the yield (65 %).
N
OH
N
OH
NO2
NO2
It should be stressed that this methodology can be applied to
obtain non-racemic ketones (3g, 3h, 3l) in good yields.
4n, 31 %
As we mentioned at the beginning, we were focused on more
complicated substrates, but to make comparison with our
previously described synthesis (Figure 3, path d), we also prepared
ketones 3e and 3i using this novel approach. Overall yields of
products 3e and 3i based on 2,4-dinitrotoluene (48 % and 60 %
respectively) are lower than in reaction between m-dinitrobenzene
INDOLES PREVIOUSLY OBTAINED BY THIS METHOD8
N
OH
NO2
N
OH
NO2
4e, 61 %
4i, 68 %
4 | J. Name., 2012, 00, 1-3
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O
O
O
to TMS (internal standard), and coupling constants in Hertz.
Multiplicities are reported as follows: singlet (s), doublet (d),
doublet of doublets (dd), triplet (t), quartet (q) and multiplet
(m). Electrospray mass spectra (ESI) were obtained on SYNAPT
G2-S HDMS.
View Article Online
DOI: 10.1039/C7NJ04919F
O2N
OH
O2N
OTHP
O2N
OTBDPS
0.25 eq PPTS
t-BuPh2SiCl, imidazole
CH2Cl2, RT, 1h
EtOH, 60°C, 80 min
NO2
NO2
NO2
6l, 94 %
5l, 94 %
3l
PPTS = pyridinium p-toluenesulfonate
SnCl2
AcOEt / EtOH, RT, 1d.
DMF was dried using calcium hydride, distilled under argon
atmosphere and stored over dried molecular sieves 4A. Silica
gel (Merck 60, 230-400 mesh) was used for column
chromatography. TLC analyses were performed on Merck
Kieselgel 60 F254 Alufolien with hexane/ethyl acetate
mixtures.
+
NBu4F / THF
RT, 2h
N
NO2
N
OTBDPS NO2
OH
N
OH
NO2
OH
7l
OH
OTBDPS
7l'
4l, 52%
72 %
Scheme 3. Synthesis of chiral indole (4l) from ketone (3l) via
ketone (6l) protected with tert-butyldiphenylsilyl (TBDPS) group
(isolated yields are given).
Aldehyde 1g was obtained from commercial N-boc-(S)-
prolinol by oxidation by Dess−Martin periodinane in similar
way to synthesis of ketones 3. Aldehyde 1h was obtained from
corresponding alcohol10a (synthesized from L-prolinol)
according to described method.10b Aldehyde 1l was obtained
from corresponding alcohol11a (obtained from commercial
ethyl L-lactate) by Swern oxidation according to described
method.11b All other chemicals were obtained from
commercial sources and used directly.
We decided to modify our starting material by introducing more
robust protecting groups (benzoyl instead of boc- and diphenyl-tert-
butylsilyl instead of tetrahydropyranyl).
Indeed, when we used N-benzoyl ketone (3h) instead of N-boc
derivative (3g), corresponding non-racemic indol 4h was obtained
in moderate yield (41 %).
Synthesis of 2,4-dinitrobenzyl alcohols (2)
Ketone (6l) bearing tert-butyldiphenylsilyl (TBDPS) group was
prepared from tetrahydropyranyl derivative (3l) according to
Scheme 3 and it was used for synthesis of the corresponding indole
(4l).
To solution of 2,4-dinitrotoluene (0.364 g, 2.0 mmol) and
aldehyde (3.0 mmol in the case of aromatic aldehydes, 1g, 1h
and 1l; 12 mmol for other aldehydes) in dry DMF (8 mL) cooled
to −30°C (bath temperature) under argon atmosphere, DBU
(10 or 25 mol %) was added via microsyringe in one portion
and the flask was put into freezer (−20 °C) for 2−3d. The
mixture was poured into water (20 mL) and extracted with
ethyl acetate (3 x 20 mL). The combined extracts were washed
with water (20 mL), brine (20 mL), dried and concentrated in
vacuo. The crude products were purified by column
chromatography on silica gel using hexane/ethyl acetate
mixtures as eluents.
In the reaction of ketone (6l) with SnCl2 mixture of isomeric
indoles (7l) and (7l’) was formed in good yield (72%).
Intramolecular migration of silyl groups is observed quite
often, especially when tert-butyldimethylsilyl group is used.
We used the mixture for deprotection step and we obtained
expected non−racemic indole (4l) in 52 % yield.
Conclusions
We have developed probably the most general method of
the synthesis of 2,4-dinitrobenzyl ketones, which are
convenient substrates for synthesis of 2-substituted 6-
nitroindoles. This methodology allows to introduce wide range
substituents into the 2-position of indole ring. Starting from
2,4-dinitrotolune and cheap, commercially available
aldehydes, we synthesized 6-nitroindoles with alkyl, cycloalkyl,
pyrrolidynyl, aryl and heteroaryl (thienyl, furyl, pyridyl)
substituents in 2-position of the indoles. We have also
obtained 1,4-bis-(6-nitro-indol-2-yl)-benzene. Starting from
non-racemic aldehydes non-racemic indoles were synthesized.
2-(2,4-Dinitrophenyl)-1-pyridin-3-yl-ethanol (2a)
Light-yellow solid (0.415 g, 72%), mp. 128 – 131 °C. IR
(KBr): 3163, 3083, 1607, 1528, 1345, 1063, 909, 835, 715, 553,
1
411 cm-1. H NMR (500 MHz, DMSO-d6): δ 8.68 (d, J = 2.3 Hz,
1H), 8.51 (d, J = 1.9 Hz, 1H), 8.44 – 8.49 (m, 2H), 7.79 (d, J = 8.5
Hz, 1H), 7.70 – 7.73 (m, 1H), 7.35 – 7.38 (m, 1H), 5.71 (d, J = 4.3
Hz, 1H), 4.86 – 4.91 (m, 1H), 3.34 – 3.39 (m, 2H). 13C NMR (125
MHz, DMSO-d6): δ 149.8, 148.5, 147.4, 146.1, 140.0, 139.7,
134.8, 133.3, 126.5, 123.3, 119.5, 70.1, 41.0. HRMS–ESI+ (m / z,
MeOH): calcd for C13H12N3O5 [M+H]+, 290.07715; found:
290.07698.
Experimental
2-(2,4-Dinitrophenyl)-1-furan-2-yl-ethanol (2b)
Yellow oil (0.361 g, 65%). IR (film): 3550, 3409, 3114,
Chemicals and instruments
1
2877, 1606, 1536, 1349, 1147, 1101, 921, 835, 734 cm-1. H
1
1H and 3C NMR spectra were recorded on a Bruker 500
NMR (500 MHz, CDCl3): δ 8.77 (d, J = 2.3 Hz, 1H), 8.33 (dd, J =
8.5 Hz, 2.3 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.41 (dd, J = 1.9 Hz,
0.9 Hz, 1H), 6.34 (dd, J = 3.3 Hz, 1.9 Hz, 1H), 6.23 – 6.25 (m,
1H), 5.05 – 5.09 (m, 1H), 3.53 – 3.60 (m, 2H), 2.20 (d. J = 3.8 Hz,
1H). 13C NMR (125 MHz, CDCl3): δ 154.5, 149.8, 146.7, 142.5,
MHz (500 MHz for 1H and 125 MHz 13C spectra), a Varian-NMR-
vnmrs500 (500 MHz for 1H and 123 MHz 13C spectra)
instruments. Chemical shifts δ are expressed in ppm referred
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J. Name., 2013, 00, 1-3 | 5
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139.6, 134.7, 126.5, 120.1, 110.4, 107.0, 67.4, 38.9. HRMS–ESI- DMSO-d6): δ 153.5, 149.9, 149.6, 145.9, 141.3, 134.8, 134.5, 126.6,
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(m / z, MeOH): calcd for C12H9N2O6 [M-H]-, 277.0461; found: 119.5, 78.4, 71.1, 70.8, 61.6, 61.4, 46.8, 46.5, 36.7, 36.3, 28.1, 25.3,
DOI: 10.1039/C7NJ04919F
277.0451.
25.0, 23.7, 23.2. HRMS–ESI+ (m / z, MeOH): calcd for C17H23N3O7Na
[M+Na]+ 404.1434; found: 404.1438
,
2-(2,4-Dinitrophenyl)-1-thiopen-2-yl-ethanol (2c)
Yellow oil (0.439 g, 75%). IR (film): 3108, 2940, 2879, 1605,
(S)-{2-[2-(2,4-Dinitr-phenyl)-1-hydroxy-ethyl]-pyrrolidin-1-yl}-
1533, 1348, 1231, 1064, 1036, 907, 836, 709 cm-1. 1H NMR (500 phenyl-methanone (2h)
MHz, CDCl3): δ 8.79 (d, J = 2.3 Hz, 1H), 8.34 (dd, J = 8.5 Hz, 2.3 Hz,
Mixture of diastereoizomers (ca. 5: 1 according to 1H NMR).
23
1H), 7.59 (d, J = 8.5 Hz, 1H), 7.28 – 7.30 (m, 1H), 6.97 – 6.99 (m, 2H), Light−yellow solid (0.754 g, 50 %), mp. 55 – 65 °C, *α+D = –90.7
5.31 – 5.34 (m, 1H), 3.47 – 3.58 (m, 2H), 2.25 – 2.27 (m. 1H). 13C (c 1.0, CHCl3). IR (KBr): 3333, 2976, 2878, 1736, 1608, 1532, 1426,
NMR (125 MHz, CDCl3): δ 149.7 146.8, 146.7, 139.7, 135.0, 127.0, 1347, 741, 721, 701 cm-1. H NMR (500 MHz, DMSO-d6): δ 8.66 –
1
126.5, 125.2, 124.2, 120.2 69.9, 42.7. HRMS–ESI- (m / z, MeOH): 8.69 (m, 1.2 H), 8.44 – 8.49 (m, 1.2 H), 7.87 (d, J = 8.5 Hz, 1H; major
calcd for C12H9N2O5S [M-H]-, 293.0232; found: 293.0219.
diastereoizomer), 7.83 (d, J = 8.3 Hz, 0.2H; minor diastereoizomer),
7.51 – 7.57 (m, 2.4H), 7.42 – 7.48 (m, 3.6H), 5.17 – 5.18 (m, 1.2H),
4.07 – 4.21 (m, 2.4H), 3.07 – 3.43 (m, 4.8H), 1.83 – 2.05 (m, 3.6H),
1.60 – 1.73 (m, 1.2H). 13C NMR (125 MHz, CDCl3): δ 169.0, 149.9,
145.9, 141.3, 137.3, 134.8, 134.5, 129.6, 128.1, 128.0, 127.1, 126.6,
119.4, 70.0, 61.2, 59.7, 50.3, 36.1, 24.7, 23.9, 20.7, 14.0. HRMS–ESI+
2-(2,4-Dinitrophenyl)-1-naphthalen-1-yl-ethanol (2d)
Yellow solid (0.528 g, 78%), mp. 156 – 159 °C. IR (KBr): 3539,
3121, 3097, 2944, 1604, 1536, 1342, 1055, 1008, 921, 836, 800,
1
779, 730, 551 cm-1. H NMR (500 MHz, DMSO-d6): δ 8.67 (d, J = 2.5
(m / z, MeOH): calcd for C19H20N3O6 [M+H]+ 386.1352; found:
Hz, 1H), 8.43 (dd, J = 8.5 Hz, 2.5 Hz, 1H), 8.24 – 8.27 (m, 1H), 7.94 –
7.97 (m, 1H), 7.84 – 7.87 (m, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.47 – 7.59
(m, 4H), 5.70 (d, J = 4.2 Hz, 1H), 5.54 – 5.58 (m, 1H), 3.46 – 3.49 (m,
2H). 13C NMR (125 MHz, DMSO-d6): δ 150.0, 146.0, 140.4, 140.3,
135.0, 133.3, 129.7, 128.7, 127.7, 126.3, 126.0, 125.5, 125.4, 123.4,
,
386.1347.
1-(2,4-Dinitrophenyl)-propan-2-ol (2i)
Orange−brown oil (0.294 g, 65%). IR (film): 3393, 3106, 2973,
123.1, 119.3, 69.2, 40.4. HRMS–ESI- (m / z, MeOH): calcd for 2932, 1605, 1535, 1455, 1349, 1117, 1069, 936, 921, 835, 740 cm-1.
C18H13N2O5 [M-H]-, 337.0824; found: 337.0823
1H NMR (500 MHz, CDCl3): δ 8.77 (d, J = 2.4 Hz, 1H), 8.38 (dd, J = 8.4
Hz, 2.4 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 4.11 – 4.18 (m, 1H), 3.25 (dd,
J = 13.5 Hz, 3.5 Hz, 1H), 3.06 (dd, J = 13.5 Hz, 8.7 Hz, 1H), 1.35 (d, J =
6.1 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 149.7, 146.6, 141.0, 134.6,
126.5, 120.2, 68.0, 41.8, 24.1. HRMS–ESI- (m / z, MeOH): calcd for
C9H9N2O5 [M-H]-, 225.0511; found: 225.0515.
2-(2,4-Dinitrophenyl)-1-phenyl-ethanol (2e)
Yellow oil (0.412 g, 71%). IR (film): 3559, 3105, 2876, 1605,
1535, 1450, 1348, 1219, 1046, 911, 835, 758, 702 cm-1. 1H NMR
(500 MHz, CDCl3): δ 8.77 (d, J = 2.4 Hz, 1H), 8.32 (dd, J = 8.4 Hz, 2.4
Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.35 – 7.39 (m, 4H), 7.30 – 7.33 (m,
1H), 5.03 – 5.06 (m, 1H), 3.47 (dd, J = 13.5 Hz, 3.6 Hz, 1H), 3.36 (dd,
J = 13.5 Hz, 8.7 Hz, 1H), 2.06 – 2.07 (m, 1H). 13C NMR (125 MHz,
1-(2,4-Dinitro-phenyl)-pentan-2-ol (2j)
Orange−brown oil (0.380 g, 75%). IR (film): 3558, 3409, 3106,
CDCl3): δ 149.8, 146.7, 143.0, 140.3, 135.0, 128.8, 128.3, 126.4, 2960, 2933, 2873, 1605, 1535, 1349, 1119, 1064, 1011, 906, 835,
125.5, 120.1, 73.9, 42.4. HRMS–ESI- (m / z, MeOH): calcd for 739 cm-1. H NMR (500 MHz, CDCl3): δ 8.76 (d, J = 2.4 Hz, 1H), 8.37
1
C14H11N2O5 [M-H]-, 287.0668; found: 287.0661.
(dd, J = 8.5 Hz, 2.4 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 3.89 – 3.95 (m,
1H), 3.28 (dd, J = 13.7 Hz, 3.2 Hz, 1H), 3.03 (dd, J = 13.7 Hz, 9.2 Hz,
1H), 1.38 – 1.61 (m, 5H), 0.97 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 149.8, 146.5, 141.4, 134.6, 126.5, 120.1, 71.6, 40.4, 40.2,
18.7, 13.9. HRMS–ESI- (m / z, MeOH): calcd for C11H13N2O5 [M-H]-,
253.0824; found: 253.0818.
2-(2,4-Dinitrophenyl)-1-cyclohexyl-ethanol (2f)
Yellow oil (0.440 g, 75%). IR (film): 3565, 3425, 3110, 2927,
2853, 1605, 1535, 1449, 1349, 835, 742 cm-1. H NMR (500 MHz,
1
DMSO-d6): δ 8.65 (d, J = 2.4 Hz, 1H), 8.44 (dd, J = 8.5 Hz, 2.4 Hz, 1H),
7.78 (d, J = 8.5 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H), 3.33 – 3.47 (m, 1H),
3.13 (dd, J = 13.3 Hz, 2.4 Hz, 1H), 2.93 (dd, J = 13.3 Hz, 10.1 Hz, 1H),
1.61 – 1.81 (m, 5H), 1.27 – 1.34 (m, 1H), 1.61 – 1.81 (m, 5H). 13C
1-(2,4-Dinitrophenyl)-3-methyl-butan-2-ol (2k)
Orange−brown oil (0.385 g, 76%). IR (film): 3069, 3426, 3106,
NMR (125 MHz, DMSO-d6): δ 150.3, 146.2, 142.8, 135.2, 126.8, 2964, 2875, 1605, 1534, 1347, 1177, 835, 739 cm-1. H NMR (500
1
119.8, 74.8, 44.5, 37.0, 29.1, 28.2, 26.6, 26.3, 26.1 HRMS–ESI- (m / z, MHz, DMSO-d6): δ 8.66 (d, J = 2.4 Hz, 1H), 8.44 (dd, J = 8.4 Hz, 2.4
MeOH): calcd for C14H17N2O5 [M-H]-, 293.1137; found: 293.1145.
Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 4.67 (d, J = 6.0 Hz, 1H), 3.10 (dd, J =
13.1 Hz, 2.5 Hz, 1H), 2.93 (dd, J = 13.1 Hz, 8.9 Hz, 1H), 3.33 – 3.38
(m, 1H), 1.61 – 1.68 (m, 1H), 0.89 – 0.92 (m, 6H),. 13C NMR (125
MHz, DMSO-d6): δ 149.8, 145.8, 142.2, 134.7, 126.4, 119.3, 75.0,
36.3, 34.0, 18.5, 17.5. HRMS–ESI- (m / z, MeOH): calcd for
C11H13N2O5 [M-H]-, 253.0824; found: 253.0823.
(S)-2-[2-(2,4-Dinitrophenyl)-1-hydroxy-ethyl]-pyrrolidine-1-
carboxylic acid tert-butyl ester (2g)
Mixture of 2 diastereoizomers. Light−yellow solid (0.447 g, 56
23
%), mp. 48 – 52 °C, *α+D = –118.9 (c 0.60, MeOH). IR (KBr): 3385,
2977, 2882, 1667, 1605, 1535, 1408, 1349, 1257, 1165, 1127, 1108,
914, 835, 740 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 8.64 – 8.70 (m,
(S)-1-(2,4-Dinitrophenyl)-3-(tetrahydropyran-2-yloxy)-butan-2-
1H), 8.46 (d, J = 8.0 Hz, 1H), 7.76– 7.83 (m, 1H), 4.98 – 5.02 (m, 1H), ol (2l)
3.82 – 3.90 (m, 1H), 3.65 – 3.73 (m, 1H), 3.32 – 3.38 (m, 1H), 3.12 –
23
Mixture of 4 diastereoizomers. Yellow oil (1.03 g, 68 %), *α+D
=
3.23 (m, 1H), 2.92 – 3.06 (m, 2H), 1.91 – 2.03 (m, 1H), 1.76 – 1.88 –34.9 (c 0.85, CHCl3). IR (film): 3416, 3105, 2944, 2871, 1605, 1536,
(m, 2H), 1.66 – 1.74 (m, 1H), 1.38 (s, 9H). 13C NMR (125 MHz, 1349, 1134, 1073, 1024, 986, 835, 741 cm-1. 1H NMR (500 MHz,
6 | J. Name., 2012, 00, 1-3
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DMSO-d6): δ 8.65 – 8.67 (m, 2.7H), 8.42 – 8.46 (m, 2.7H), 7.80 – mixture was diluted with ethyl acetate (50 mL), VwieawsAhrteicdle Ownilitnhe
DOI: 10.1039/C7NJ04919F
7.85 (m, 2.7H), 4.89 – 4.92 (m, 1.8H), 4.85 – 4.88 (m, 0.9H), 4.67 – aqueous NaHCO3 (10 mL), water (10 mL), dried and
4.74 (m, 2.7H), 3.77 – 3.86 (m, 2.7H), 3.48 – 3.55 (m, 1.8H), 3.40 – concentrated in vacuo. Pure products were obtained according
1
3.46 (m, 2.7H), 3.34 – 3.39 (m, 1.0H), 3.03 – 3.20 (m, 2.3H), 2.90 – to H NMR and the products were used for next step without
3.00 (m, 2.3H), 1.68 – 1.80 (m, 2.7H), 1.60 – 1.66 (m, 3.0H), 1.40 – further purification.
1.52 (m, 11.7H), 1.08 – 1.19 (m, 9.9H). 13C NMR (125 MHz, DMSO-
2-(2,4-Dinitrophenyl)-1-naphthalen-1-yl-ethanone (3d)
Light-brown solid (0.206 g, 61%), mp. 195 – 196 °C. IR
(KBr): 3099, 3046, 2944, 2867, 1679, 1605, 1528, 1344, 1318,
1233, 1173, 1092, 944, 909, 803, 778, 724, 709, 649, 623, 488
d6): δ 149.9, 145.8, 141.7, 141.6, 134.8, 134.7, 134.5, 126.3, 126.2,
119.3, 119.2, 98.7, 98.3, 95.5, 95.0, 76.9, 75.5, 74.0, 73.6, 73.5,
73.4, 72.7, 72.0, 61.8, 61.7, 61.6, 60.0, 35.7, 34.7, 33.9, 30.7, 30.6,
30.5, 30.4, 25.0, 19.3, 19.2, 19.1, 17.5, 16.1, 15.0, 14.0, 13.7. HRMS–
1
cm-1. H NMR (500 MHz, DMSO-d6): δ 8.86 (d, J = 2.4 Hz, 1H),
ESI+ (m / z, MeOH): calcd for C15H20N2O7Na [M+Na]+ 363.1168;
,
8.62 (dd, J = 8.3 Hz, 2.4 Hz, 1H), 8.43– 8.46 (m, 1H), 8.34 – 8.37
(m, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.04 – 8.07 (m, 1H), 7.97 – 7.99
(m, 1H), 7.69 – 7.73 (m, 1H), 7.59 – 7.64 (m, 2H), 5.16 (s, 2H).
found: 363.1167.
(E)-1-(2,4-Dinitro-phenyl)-4-phenyl-but-3-en-2-ol (2m)
Light-yellow solid (0.383 g, 61%), mp. 97 – 100 °C. IR (KBr): 13C NMR (125 MHz, DMSO-d6): δ 198.6, 148.8, 146.8, 137.9,
3548, 3421, 3115, 3099, 3025, 2943, 2866, 1722, 1607, 1534, 1341, 135,5, 134.1, 133.5, 133.2, 129.4, 128.8, 128.6, 128.0, 127.8,
1
1061, 1023, 968, 920, 906, 835, 756, 739, 716, 695 cm-1. H NMR 126.5, 125.1, 124.8, 120.1, 46.3. HRMS–ESI+ (m / z, MeOH):
(500 MHz, DMSO-d6): δ 8.67 (d, J = 2.5 Hz, 1H), 8.46 (dd, J = 8.4Hz, calcd for C18H12N2O5Na [M+Na]+ 359.0644; found: 359.0635.
,
2.5 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.22 – 7.42 (m, 5H), 6.51 (d, J =
15.9 Hz, 1H), 6.32 (dd, J = 15.9 Hz, 5.9 Hz, 1H), 5.32 (d, J = 4.6 Hz,
1H), 4.38 – 4.43 (m, 1H), 3.28 (dd, J = 13.3 Hz, 4.5 Hz, 1H), 3.19 (dd,
J = 13.3 Hz, 8.1Hz, 1H). 13C NMR (125 MHz, DMSO-d6): δ 149.9,
2-(2,4-Dinitrophenyl)-1-phenyl-ethanone (3e)
Compound previously described.8 Light–yellow solid (0.154
146.0, 140.3, 136.4, 134.8, 132.6, 129.0, 128.6, 127.5, 126.4, 126.3,
g, 68%), mp. 133 – 136 °C, lit.8 133 – 135 °C. 1H NMR (500 MHz,
CDCl3): δ 8.99 (d, J = 2.4 Hz, 1H), 8.45 (dd, J = 8.3 Hz, 2.4 Hz,
119.4, 70.9. HRMS–ESI- (m / z, MeOH): calcd for C16H13N2O5 [M-H]-,
313.0824; found: 313.0813.
1H), 8.01 – 8.04 (m, 2H), 7.63 – 7.67 (m, 1H), 7.59 (d, J = 8.3 Hz,
1H), 7.51 – 7.55 (m, 2H), 4.87 (s, 2H). 13C NMR (125 MHz,
2-(2,4-Dinitro-phenyl)-1-{4-[2-(2,4-dinitro-phenyl)-1-hydroxy-
ethyl]-phenyl}-ethanol (2n)
CDCl3): δ 193.9, 149.2, 147.4, 137.6, 135.9, 134.9, 134.0, 128.9,
128.3, 127.3, 120.7, 44.1.
2,4-Dinitrotoluene was used at 100 % excess. Yellow solid
(0.867 g, 58%), mp. 194 – 196 °C. IR (KBr): 3572, 3099, 1608,
1538, 1518, 1449, 1346, 1040, 923, 905, 852, 836, 781, 733,
563 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 8.68 (d, J = 2.3, 2H), 8.45
(dd, J = 8.5 Hz, 2.3 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.31 (s, 4H), 5.51
(d, J = 4.6 Hz, 2H), 4.76 – 4.81 (m, 2H), 3.24 – 3.33 (m, 4H). 13C NMR
(125 MHz, DMSO-d6): δ 149.8, 146.0, 143.7, 140.6, 134.8, 126.4,
125.4, 119.4, 72.0, 41.6. HRMS–ESI+ (m / z, MeOH): calcd for
2-(2,4-Dinitrophenyl)-1-cyclohexyl-ethanone (3f)
Light−Brown oil (0.284 g, 97%). IR (film): 3113, 2932, 2855,
1711, 1605, 1536, 1449, 1348, 1146, 1067, 1000, 910, 836,
1
810, 719 cm-1. H NMR (500 MHz, DMSO-d6): δ 8.76 (bs, 1H),
8.50 – 8.54 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 4.48 (s, 2H), 2.55 –
2.60 (m, 1H), 1.88 – 1.93 (m, 2H), 1.71 – 1.76 (m, 2H), 1.61 –
1.67 (m, 1H), 1.27 – 1.34 (m, 4H), 1.14 – 1.22 (m, 1H). 13C NMR
(125 MHz, DMSO-d6): δ 207.9, 148.7, 146.6, 137.7, 135.1,
127.4, 119.8, 49.4, 45.0, 27.8, 25.3, 25.0 HRMS–ESI+ (m / z,
C22H18N4O10Na [M+Na]+ 521.0921; found: 521.0912.
,
4-[2-(2,4-Dinitrophenyl)-1-hydroxy-ethyl]-benzaldehyde (2n’)
Yellow solid (0.320 g, 33%), mp. 184 – 187 °C. IR (KBr): 3433,
3091, 1685, 1671, 1603, 1526, 1345, 1211, 1053, 842, 834, 787,
MeOH): calcd for C14H16N2O5Na [M+Na]+ 315.0957; found:
,
315.0952.
1
738, 720, 671, 548 cm-1. H NMR (500 MHz, DMSO-d6): δ 10.0 (s,
1-(2,4-Dinitrophenyl)-propan-2-one (3i)
1H), 8.68 (d, J = 2.3, 1H), 8.45 (dd, J = 8.5 Hz, 2.3 Hz, 1H), 7.55 –
7.58 and 7.87 –7.90 (AA`XX`, 4H), 7.78 (d, J = 8.5 Hz, 1H), 5.76 (d, J
= 4.6 Hz, 1H), 4.90 – 4.95 (m, 1H), 3.36 – 3.49 (m, 1H), 3.27 – 3.32
(m, 1H). 13C NMR (125 MHz, DMSO-d6): δ 192.7, 151.5, 149.8, 146.1,
140.0, 135.3, 134.8, 129.5, 126.5, 126.3, 119.5, 71.8, 41.1. HRMS–
ESI- (m / z, MeOH): calcd for C15H11N2O6 [M-H]-, 315.0617; found:
315.0624.
Compound previously described.8 Orange solid (0.265 g,
93%), mp. 63 – 66 °C, lit.8 65 − 67°C. 1H NMR (500 MHz, CDCl3):
δ 8.96 (d, J = 2.4 Hz, 1H), 8.43 (dd, J = 8.3 Hz, 2.4 Hz, 1H), 7.51
(d, J = 8.3 Hz, 1H), 4.28 (s, 2H), 2.38 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 201.9, 148.8, 147.3, 137.0, 134.8, 127.4, 120.7, 48.4,
30.1.
1-(2,4-Dinitrophenyl)-pentan-2-one (3j)
Synthesis of 2,4-dinitrobenzyl ketones (3) by Jones oxidation
Yellow solid (0.242 g, 96%), mp. 73 – 74°C. IR (KBr): 3110,
2967, 2935, 2876, 1706, 1609, 1525, 1347, 1123, 1060, 911,
836, 707, 488, 429 cm-1. 1H NMR (500 MHz, CDCl3): δ 8.95 (d, J
= 2.2 Hz, 1H), 8.43 (dd, J = 8.3 Hz, 2.2 Hz, 1H), 7.50 (d, J = 8.3
Hz, 1H), 4.25 (s, 2H), 2.62 (t, J = 7.3 Hz, 2H), 1.65 – 1.73 (m,
2H), 0.97 (t, J = 7.3 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 204.2,
148.8, 147.3, 137.1, 134.8, 127.3, 120.6, 47.7, 44.9, 17.1, 13.6.
To solution of 2,4-dinitrobenzylalcohols
2 (1.0 mmol) in
acetone (10 mL), solution of CrO3 (obtained by dissolving 2.67
g CrO3 and 2.3 mL H2SO4 in water and diluted to 10 mL with
water) was added in 3 portions (0.2 mL every 20 min) at room
temperature. After adding the last portion, the mixture was
stirred at room temperature for 20 minutes. The reaction
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HRMS–ESI- (m / z, MeOH): calcd for C11H11N2O5 [M-H]-, 43.5. HRMS–ESI+ (m / z, MeOH): calcd for C12H8N2O6Na
View Article Online
DOI: 10.1039/C7NJ04919F
251.0668; found: 251.0684.
[M+Na]+ 299.0280; found: 299.0277.
,
1-(2,4-Dinitro-phenyl)-3-methyl-butan-2-one (3k)
Yellow solid (0.251 g, ~100%), mp. 74 – 77°C. IR (KBr):
2-(2,4-Dinitro-phenyl)-1-thiophen-2-yl-ethanone (3c)
White solid (0.222 g, 76%), mp. 119 – 120 °C . IR (KBr): 3109,
1
3101, 2976, 2929, 2877, 1708, 1604, 1528, 1346, 1043, 910, 1659, 1602, 1535, 1522, 1408, 1342, 1225, 1062, 945, 837, 777,
835, 735, 712 cm-1.1H NMR (500 MHz, CDCl3): δ 8.95 (d, J = 2.2 738, 726, 700 cm-1. H NMR (500 MHz, CDCl3): δ 8.97 (d, J = 2.2 Hz,
Hz, 1H), 8.42 (dd, J = 8.4 Hz, 2.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 1H), 8.45 (dd, J = 8.4 Hz, 2.2 Hz, 1H), 7.88 (d, J = 3.8 Hz, 1H), 7.73 (d,
4.34 (s, 2H), 2.83 (sep, J = 7.1 Hz, 1H), 1.23 (d, J = 7.1 Hz, 6H). J = 5.0 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.20 – 7.22 (m, 1H), 4.80 (s,
13C NMR (125 MHz, CDCl3): δ 207.9, 149.0, 147.2, 137.4, 134.8, 2H). 13C NMR (125 MHz, CDCl3): δ 186.4, 147.4, 142.6, 136.7, 135.0,
127.2, 120.6, 45.7, 41.2, 18.1. HRMS–ESI- (m / z, MeOH): calcd 134.8, 132.7, 128.4, 127.3, 120.6, 44.3. HRMS–ESI+ (m / z, MeOH):
for C11H11N2O5 [M-H]-, 251.0668; found: 251.0677.
calcd for C12H8N2O5SNa [M+Na]+ 315.0052; found 315.0045.
,
2-(2,4-Dinitrophenyl)-1-{4-[2-(2,4-dinitro-phenyl)-acetyl]-
phenyl}-ethanone (3n)
(S)-2-[2-(2,4-Dinitrophenyl)-acetyl]-pyrrolidine-1-carboxylic
acid tert-butyl ester (3g)
23
1.1 mL of solution of CrO3 was added. Light
–brown solid
Yellow oil (0.315 g, 83 %), *α+D = –122.7 (c 0.35, MeOH). IR
(0.362 g, 73%), mp. 217 °C (decomp.). IR (KBr): 3109, 1694, (film): 3104, 2978, 1694, 1606, 1537, 1396, 1348, 1163, 1124, 1065,
1685, 1603, 1533, 1403, 1340, 1215, 991, 824, 788, 728, 706, 909, 836, 734 cm-11H NMR (500 MHz, DMSO-d6); mixture of
596 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 8.85 (bs, 2H), 8.59 – rotamers : δ 8.77 (bs, 1H), 8.50 – 8.56 (m, 1H), 7.77 (d, J = 8.5 Hz,
8.63 (m, 2H), 8.27 (s, 4H), 7.93 (d, J = 8.4 Hz, 2H), 5.15 (s, 4H). 1H), 4.37 – 4.56 (m, 3H), 3.34 – 3.42 (m, 2H), 2.14 – 2.31 (m, 1H),
13C NMR (125 MHz, DMSO-d6): δ 195.0, 148.6, 146.9, 139.4, 1.94 – 2.05 (m, 1H), 1.72 – 1.91 (m, 2H), 1.41 (s, 3H), 1.35 (s, 6H).
137.6, 135.5, 128.6, 127.7, 120.1, 43.8. HRMS–ESI- (m / z, 13C NMR (125 MHz, DMSO-d6); mixture of rotamers: δ 204.4, 148.9,
MeOH): calcd for C22H13N4O10 [M-H]-, 493.0632; found: 136.7, 136.4 135.1, 134.9, 127.6, 119.9, 79.1, 64.6, 64.4, 46.5, 46.4,
493.0634.
43.6, 43.4, 29.1, 28.0, 27.9, 23.9, 23.0. HRMS–ESI+ (m / z, MeOH):
calcd for C17H21N3O7Na [M+Na]+ 402.1278; found: 402.1272.
,
Oxidation 2,4-dinitrobenzyl alcohols by Dess-Martin
periodinane
(S)-{2-[2-(2,4-Dinitro-phenyl)-1-hydroxy-ethyl]-pyrrolidin-1-yl}-
phenyl-methanone (3h)
21
To solution of 2,4-dinitrobenzylalcohols
2
(1.0 mmol) in
Light−yellow solid (0.337 g, 88 %), mp. 50 – 54 °C, *α+D = –
CH2Cl2 (2 mL) cooled to −5°C under argon atmosphere, solution 119.6 (c 1.0, CHCl3). IR (KBr): 3103, 2975, 2952, 2877, 1730, 1626,
of Dess-Martin periodinane (0.49 g; 1.15 mmol) in CH2Cl2 (3.5 1536, 1414, 1346, 1146, 1065, 908, 835, 724, 701 cm-1. 1H NMR (500
mL) was added in 5 minutes keeping temperature below 3°C. MHz, DMSO-d6): δ 8.78 (d, J = 2.3 Hz, 1H), 8.53 (dd, J = 8.4 Hz, 2.3
When addition was completed, the cooling bath was removed Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.56 – 7.59 (m, 2H), 7.44 – 7.51 (m,
and the reaction mixture was stirred for 60 – 80 minutes at RT. 3H), 4.74 – 4.77 (m, 1H), 4.53 – 4.65 (m, 2H), 3.59 – 3.64 (m, 1H),
The mixture was concentrated and subject to column 3.50 – 3.55 (m, 1H), 2.27 – 2.34 (m, 1H), 1.96 – 2.03 (m, 1H), 1.87–
chromatography on silica gel. Mixtures hexane / CH2Cl2 or pure 1.93 (m, 2H). 13C NMR (125 MHz, DMSO-d6): δ 203.8, 168.6, 148.9,
CH2Cl2 was used as eluent.
146.7, 136.7, 135.9, 135.2, 130.2, 128.2, 127.5, 127.1, 119.9, 64.8,
49.8, 43.8, 27.6, 25.0. HRMS–ESI+ (m / z, MeOH): calcd for
C19H18N3O6 [M+H]+ 384.1196; found: 384.1196.
2-(2,4-Dinitro-phenyl)-1-pyridin-3-yl-ethanone (3a)
,
Y
ellow solid (0.187 g, 65%), mp. 135 – 139 °C. IR (KBr):
3042, 2928, 1686, 1603, 1586, 1537, 1521, 1342, 1232, 837,
(S)-1-(2,4-Dinitrophenyl)-3-(tetrahydro-pyran-2-yloxy)-butan-
722, 700 cm-1. 1H NMR (500 MHz, CDCl3): δ 9.28 (d, J = 1.6 Hz, 2-one (3l)
1H), 9.03 (d, J = 2.2 Hz, 1H), 8.86 – 8.89 (m, 1H), 8.49 (dd, J =
Mixture of diastereoizomers. Yellow solid (0.309 g, 91 %), mp.
23
8.4 Hz, 2.2 Hz, 1H), 8.28 – 8.32 (m, 1H), 7.62 (d, J = 8.4 Hz, 1H), 50 – 65 °C, *α+D = –33.8 (c 1.0, CHCl3). IR (KBr): 2941, 1730, 1606,
7.48 – 7.52 (m, 1H), 4.87 (s, 2H). 13C NMR (125 MHz, CDCl3): δ 1537, 1345, 1125, 1034, 978, 736, 717 cm-1. 1H NMR (500 MHz,
192.9, 154.3, 149.6, 136.6, 135.6, 135.0, 131.4, 127.6, 123.9, DMSO-d6): δ 8.76 – 8.78 (m, 1.3H), 8.51 – 8.56 (m, 1.3H), 7.78 –
120.8, 44.4. HRMS–ESI- (m / z, MeOH): calcd for C13H8N3O5 [M- 7.84 (m, 1.3H), 4.71 – 4.74 (m, 1.3H), 4.55 – 4.63 (m, 1.8H), 4.45 –
H]-, 286.0464; found: 286.0462.
4.49 (m, 0.7H), 4.36 – 4.41 (m, 0.7H), 4.21– 4.25 (m, 0.7H), 3.79 –
3.84 (m, 1.3H), 3.42– 3.51 (m, 1.3H), 1.69 – 1.82 (m, 2.7H), 1.58 –
1.63 (m, 0.7H), 1.48 – 1.55 (m, 4.6H), 1.37 (d, J = 7.0 Hz, 2.1H), 1.29
(d, J = 6.8 Hz, 1.8H). 13C NMR (125 MHz, DMSO-d6): δ 207.2, 206.6,
148.9, 148.6, 146.7, 146.6, 137.4, 137.3, 135.4, 135.2, 127.5, 127.4,
120.0, 119.9, 98.0, 97.9, 77.5, 76.9, 63.0, 61.8, 43.0, 42.8, 30.5,
30.1, 24.9, 24.8, 19.7, 19.0, 17.9, 16.4. HRMS–ESI+ (m / z, MeOH):
2-(2,4-Dinitro-phenyl)-1-furan-2-yl-ethanone (3b)
Yellow solid (0.223 g, 81%), mp. 136 – 138 °C. IR (KBr):
3099, 1666, 1602, 1523, 1464, 1393, 1347, 1261, 997, 771, 729
cm-1. H NMR (500 MHz, CDCl3): δ 8.97 (d, J = 2.3 Hz, 1H), 8.45
(dd, J = 8.4 Hz, 2.3 Hz, 1H), 7.66 (d, J = 1.5 Hz, 1H), 7.61 (d, J =
8.4 Hz, 1H), 7.32 (d, J = 3.7 Hz, 1H), 6.62 (dd, J = 3.7 Hz, 1.5 Hz,
1H), 4.73 (s, 2H). 13C NMR (125 MHz, CDCl3): δ 182.7, 151.8,
149.2, 147.4, 146.9, 136.5, 135.0, 127.3, 120.6, 118.0, 112.8,
calcd for C15H20N2O7Na [M+Na]+ 363.1168; found: 363.1167.
,
(E)-1-(2,4-Dinitro-phenyl)-4-phenyl-but-3-en-2-one (3m)
Light−yellow solid (0.249 g, 80%), mp. 139 – 141 °C. IR (KBr):
8 | J. Name., 2012, 00, 1-3
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3105, 2933, 1668, 1610, 1535, 1347, 1177, 1086, 977, 919, 836,
2-Naphthalen-1-yl-6-nitro-indol-1-ol (4d)
Orange solid (0.088 g, 72%), mp. 160 – 162 °C. IR (KBr):
View Article Online
DOI: 10.1039/C7NJ04919F
1
750, 690 cm-1. H NMR (500 MHz, DMSO-d6): δ 8.79 (d, J = 2.2 Hz,
1H), 8.56 (dd, J = 8.4Hz, 2.2 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.76 – 3217, 1605, 1498, 1339, 1273, 1109, 1060, 877, 771, 724, 685
7.82 (m, 3H), 7.46 – 7.49 (m, 3H), 7.04 (d, J = 16.3 Hz, 1H), 4.74 (s, cm-1.1H NMR (500 MHz, DMSO-d6): δ 11.68 (bs, 1H), 8.37 (bs,
2H). 13C NMR (125 MHz, DMSO-d6): δ 194.7, 148.8, 146.7, 143.6, 1H), 8.11 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.98 (dd, J
137.6, 135.3, 134.1, 130.8, 129.0, 128.6, 127.6, 125.6, 120.0, 44.9. = 8.8 Hz, 2.1 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.8 Hz,
HRMS–ESI+ (m / z, MeOH): calcd for C16H12N2O5Na [M+Na]+ 1H), 7.74 – 7.76 (m, 1H), 7.66– 7.69 (m, 1H), 7.55 – 7.62 (m,
,
335.0644; found: 335.0634.
2H), 6.81 (s, 1H). 13C NMR (125 MHz, DMSO-d6): δ 142.1,
141.6, 133.2, 132.4, 131,2, 129.6, 129.1, 128.3, 127.5, 127.0,
126.9, 126.3, 125.6, 125.2, 120.8, 114.6, 105.4, 99.7. HRMS–
Synthesis of 2-substituted 6-nitroindols
ESI+ (m / z, MeOH): calcd for C18H12N2O3Na [M+Na]+ 327.0746;
,
To solution of ketones (3) (0.40 mmol) in ethyl acetate (2.0
mL), ethanol (0.20 mL) and anhydrous SnCl2 (0.32 g; 1.69
mmol) were added subsequently and the solution was stirred
overnight at room temperature. The mixture was concentrated
and the residue was subject to column chromatography on
silica gel. Hexane / ethyl acetate (usually 4/1) was used as
eluent.
found: 327.0737.
2-Cyclohexyl-6-nitro-indol-1-ol (4f).
Yellow–orange solid, mp. 110 – 111 °C. IR (KBr): 3314,
2922, 2852, 1608, 1501, 1462, 1382, 1319, 1110, 1064, 870,
816, 766, 727 cm-1.1H NMR (500 MHz, DMSO-d6): δ 11.53 (s,
1H), 8.21 (d, J = 2.2 Hz, 1H), 7.86 (dd, J = 8.6 Hz, 2.2 Hz, 1H),
7.62 (d, J = 8.6 Hz, 1H), 6.31 (s, 1H), 2.90 – 2.96 (m, 1H), 2.02 –
2.06 (m, 2H), 1.80 – 1.84 (m, 2H), 1.71 – 1.75 (m, 1H), 1.37 –
1.49 (m, 4H), 1.23 – 1.32 (m, 1H). 13C NMR (125 MHz, DMSO-
d6): δ 150.4, 141.2, 131.6, 127.7, 119.9, 114.1, 104.6, 93.5,
34.4, 31.6, 25.7, 25.5. HRMS–ESI+ (m / z, MeOH): calcd for
6-Nitro-2-pyridin-3-yl-indol-1-ol (4a). After 1d at room
temperature the mixture was evaporated to dryness, 10 %
aqueous KF (8 mL) was added and the mixture was stirred at
room temperature for 15 min. The mixture was extracted with
ethyl acetate (4 x 15 mL), dried and evaporated. The crude
product was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 50/1 was used as eluen). Brown solid (0.051 g,
50%), mp. > 310 °C. IR (KBr): 3334, 3201, 3103, 1598, 1503,
1469, 1387, 1332, 1284, 1227, 1186, 1151, 1122, 1088, 1029,
873, 814, 770, 726, 701, 635 cm-1. 1H NMR (500 MHz, DMSO-
d6): δ 12.04 (bs, 1H), 9.14 (d, J = 1.7 Hz, 1H), 8.66 (dd, J = 4.7
Hz, 1.7 Hz, 1H), 8.33 – 8.36 (m, 2H), 7.94 (dd, J = 8.8 Hz, 2.1 Hz,
1H), 7.79 (d, J = 8.8 Hz, 1H), 7.57 – 7.60 (m, 1H), 7.04 (bs, 1H).
13C NMR (125 MHz, DMSO-d6): δ 149.6, 148.6, 142.5, 139.3,
135.2, 133.5, 127.3, 125.7, 123.7, 121.0, 114.9, 105.4, 97.9.
C14H16N2O3Na [M+Na]+ 283.1059; found: 283.1051.
,
(S)-[2-(1-Hydroxy-6-nitro-1H-indol-2-yl)-pyrrolidin-1-yl]-
phenyl-methanone (4h)
23
Yellow solid (0.057 g, 41 %), mp. 246 – 249 °C, *α+D
=
29.2 (c 0.60, pyridine). IR (KBr): 2707, 1733, 1588, 1563, 1497,
1450, 1329, 1279, 1114, 823, 727 cm-1. 1H NMR (500 MHz,
DMSO-d6, 333K): δ 11.64 (bs, 1H), 8.23 (bs, 1H), 7.85 (dd, J =
8.7 Hz, 2.0 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.42 – 7.62 (m, 5H),
6.43 (bs, 1H), 5.56 (bs, 1H), 3.75 – 3.81 (m, 1H), 3.52 (bs, 1H),
2.42 (bs, 1H), 2.06 (bs, 1H), 1.96 (bs, 2H). 13C NMR (125 MHz,
DMSO-d6): δ 168.7, 146.3, 141.4, 136.7, 131.9, 130.0, 128.2,
127.1, 126.2, 120.1, 114.2, 104.7, 94.2, 53.1, 49.6, 31.5, 24.4.
HRMS–ESI+ (m / z, MeOH): calcd for C13H10N3O3 [M+H]+
,
256.0722; found: 256.0721.
HRMS–ESI+ (m / z, MeOH): calcd for C19H18N3O4 [M+H]+
352.1297; found: 352.1294.
,
2-Furan-2-yl-6-nitro-indol-1-ol (4b)
Deep red solid (0.053 g, 54%), mp. 201 – 203 °C. IR (KBr):
3281, 1602, 1499, 1456, 1433, 1321, 1282, 1226, 1094, 1013,
868, 814, 776, 739 cm-1. 1H NMR (500 MHz, (DMSO-d6): δ
12.07 (s, 1H), 8.28 (bs, 1H), 7.91 – 7.94 (m, 2H), 7.74 (d, J = 8.8
Hz, 1H), 7.22 (d, J = 3.4, 1H), 6.84 (s, 1H), 6.74 – 6.76 (m, 1H).
13C NMR (125 MHz, DMSO-d6): δ 144.3, 143.9, 142.1, 133.6,
132.9, 127.6, 120.7, 115.0, 112.3, 110.9, 105.0, 94.5. HRMS–EI
(m / z): calcd for C12H8N2O4 (M+·), 244.0484; found: 244.0492.
6-Nitro-2-propyl-indol-1-ol (4j)
Yellow solid (0.051 g, 58%), mp. 96 – 97 °C. IR (film): 3256,
2956, 2930, 1612, 1584, 1504, 1336, 1322, 1277, 1094, 1059,
882, 810, 765, 728 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 11.53
(s, 1H), 8.21 (d, J = 2.2 Hz, 1H), 7.86 (dd, J = 8.6 Hz, 2.2 Hz, 1H),
7.62 (d, J = 8.6 Hz, 1H), 6.35 (d, J = 0.5 Hz, 1H), 2.80 (t, J = 7.4
Hz, 2H), 1.71 – 1.79 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H). 13C NMR
(125 MHz, DMSO-d6): δ 145.5, 141.2, 131.6, 127.7, 119.7,
6-Nitro-2-thiophen-2-yl-indol-1-ol (4c)
114.1, 104.5, 95.5, 27.1, 20.9, 13.7. C11H12N2O3Na [M+Na]+
243.0746; found: 243.0739.
,
Orange solid (0.063 g, 60%), mp. 195 – 198 °C. IR (KBr):
3266, 3103, 1606, 1508, 1483, 1317, 1281, 1220, 1135, 1064,
1052, 810, 768, 722, 697 cm-1. 1H NMR (500 MHz, DMSO-d6): δ
12.17 (bs, 1H), 8.26 (d, J = 1.9 Hz, 1H), 7.92 (dd, J = 8.8 Hz, 1.9
Hz, 1H), 7.86 – 7.88 (m, 1H), 7.77 – 7.79 (m, 1H), 7.70 (d, J = 8.8
Hz, 1H). 7.25 – 7.27 (m, 1H), 6.97 (bs, 1H). 13C NMR (125 MHz,
DMSO-d6): δ 141.8, 137.0, 132.7, 130.2, 128.7, 127.9, 127.8,
127.7, 120.3, 115.1, 105.0, 95.3. HRMS–EI (m / z): calcd for
C12H8N2O3S (M+·), 260.0256; found: 260.0260.
2-Isopropyl-6-nitro-indol-1-ol (4k)
Orange solid (0.044 g, 50%), mp. 112 – 113°C (decomp.).
IR (KBr): 3244, 2971, 1615, 1499, 1462, 1323, 1270, 1217,
1102, 1051, 871, 818, 728 cm-1. H NMR (500 MHz, DMSO-d6):
1
δ 11.55 (s, 1H), 8.23 (d, J = 2.2 Hz, 1H), 7.87 (dd, J = 8.8 Hz, 2.2
Hz, 1H), 7.63 (d, J = 8.8 Hz, 1H), 6.34 (s, 1H), 3.26 (sep, J = 6.8
Hz, 1H), 1.34 (d, J = 6.8 Hz, 6H). 13C NMR (125 MHz, DMSO-d6):
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J. Name., 2013, 00, 1-3 | 9
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Journal Name
δ 151.8, 141.7, 132.3, 128.1, 120.4, 114.6, 105.0, 93.7, 25.5, DMSO-d6): δ 8.77 (d, J = 2.4 Hz, 1H), 8.52 (dd, J = 8.4 Hz, 2.4 Hz,
View Article Online
21.9. HRMS–ESI+ (m / z, MeOH): calcd for C11H12N2O3Na 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.63 − 7.69 (m, 4H), 7.43 − 7.53 (m,
DOI: 10.1039/C7NJ04919F
[M+Na]+ 243.0746; found: 243.0736.
6H), 4.57 (d, J = 18.5 Hz, 1H), 4.51 (d, J = 18.5 Hz, 1H), 4.40 (q, J
= 6.8 Hz, 1H), 1.23 (d, J = 6.8 Hz, 3H), 1.08 (s, 9H). 13C NMR
(125 MHz, DMSO-d6): δ 206.7, 148.7, 146.7, 137.1, 135.3,
135.2, 132.9, 132.3, 130.1, 130.0, 127.9, 127.8, 127.5, 119.9,
74.9, 42.7, 26.7, 20.0, 18.8. HRMS–ESI+ (m / z, MeOH): calcd
,
(E)-6-Nitro-2-styryl-indol-1-ol (4m)
Red solid (0.052 g, 46%), mp. 186 – 191°C (decomp.). IR
(KBr): 3415, 2962, 1629, 1604, 1492, 1318, 1262, 1111, 1060,
959, 869, 815, 687 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 11.92
(s, 1H), 8.24 (d, J = 2.2 Hz, 1H), 7.89 (dd, J = 8.7 Hz, 2.2 Hz, 1H),
7.67 – 7.70 (m, 3H), 7.63 (d, J = 16.6 Hz, 1H), 7.34 – 7.39 (m,
2H), 7.42 – 7.45 (m, 2H), 6.94 (s, 1H). 13C NMR (125 MHz,
for C22H28N2O6SiNa [M+Na]+ 515.1614; found: 515.1610.
,
Mixture of (7l) and (7l’)
Mixture of regioisomers (~1/1 ratio according to H NMR)
1
DMSO-d6): δ 141.7, 141.2, 136.2, 133.5, 132.5, 128.9, 128.7, was obtained. Yellow oil (0.162 g, 72 %). IR (film): 3396, 3072,
127.7, 126.8, 120.3, 114.9, 114.8, 104.9, 95.4. HRMS–ESI+ (m / 2959, 2931, 2858, 1612, 1589, 1506, 1471, 1428, 1332, 1113,
1
z, MeOH): calcd for C16H12N2O3Na [M+Na]+ 303.0746; found: 1036, 950, 821, 739, 700, 607, 505, 489 cm-1. H NMR (500
,
303.0740.
MHz, DMSO-d6): δ 11.58 (s, 1H), 8.20 (s, 1H), 7.88 (dd, J = 8.8
Hz, 2.0 Hz, 1H), 7.65 –7.73 (m, 8H), 7.52 –7.56 (m, 2H), 7.37 –
7.50 (m, 12H), 7.32 – 7.35 (m, 2H), 6.58 (bs, 1H), 6.55 (bs, 1H),
5.21 (q, J = 6.2 Hz, 1H), 4.03 (q, J = 7.1 Hz, 1H), 1.42 (d, J = 6.4
Hz, 3H), 1.04 (s, 9H), 0.92–0.99 (m, 12H). 13C NMR (125 MHz,
DMSO-d6): δ 148.2, 136.3, 135.2, 135.1, 134.4, 133.2, 132.6,
131.8, 130.0, 129.9, 129.1, 127.8, 127.7, 127.4, 127.3, 120.6,
114.1, 104.9, 94.1, 64.2, 26.7, 26.5, 24.1, 18.8. 18.6. HRMS–
1,4-bis-(6-nitro-indol-1-ol-2-yl)-benzene (4n)
0.65 g of SnCl2 was used. (IND-353). Brown solid (0.054 g,
31%), mp. > 310 °C. IR (KBr): 3105, 1606, 1498, 1472, 1461,
1385, 1319, 1282, 1086, 1033, 862, 822, 779, 741, 727 cm-1. 1H
NMR (500 MHz, DMF-d7): δ 12.32 (bs, 2H), 8.44 (bs, 2H), 7.98 –
8.03 (m, 6H), 7.83 (d, J = 8.7 Hz, 2H), 7.07 (bs, 2H). 13C NMR
(125 MHz, DMF-d7): δ 143.6, 142.9, 134.9, 131.0, 129.2, 128.7,
121.5, 115.7, 106.2, 98.7. HRMS–ESI+ (m / z, MeOH): calcd for
ESI+ (m
/
z, MeOH): calcd for C26H28N2O4SiNa[M+Na]+
,
483.1716; found: 483.1723.
C22H14N4O6Na [M+Na]+ 453.0811; found: 453.0811.
,
Removing of TBDPS group. Synthesis of (S)-2-(2-hydroxy-
propyl)-6-nitro-indol-1-ol (4l)
Removing of THP group. Synthesis of (S)-1-(2,4-
dinitrophenyl)-3-hydroxy-butan-2-one (5l)
Solution of ketone 3l (0.28 g, 0.83 mmol) and pyridinium p-
To solution of mixture of (7l) and (7l’) in THF (2 mL) 1M
toluenesulfonate (0.052 g; 0.21 mmol; 0.25 eq.) in EtOH was TBAF in THF (2 mL) was added and the mixture was stirred at
stirred at 60°C for 80 minutes. The mixture was cooled, room temperature for 2h. 2M HCl was added to pH=4 and the
concentrated and the concentrated mixture was subject to mixture was extracted with ethyl acetate (3 x 10 mL). The
column chromatography on silica gel. Hexane / ethyl acetate, combined extracts were dried and evaporated. The crude
2/1, next 1/1 was used as eluent. Pure product (0.196 g, 94 %) product was purified by column chromatography on silica gel
was obtained. (IND-314). Light−yellow solid, mp. 80 – 83 °C, (hexane/ethyl acetate, 1/1, was used as eluent). Yellow solid
19
1
22
*α+D = –29.5 (c 1.1, CHCl3). H NMR (500 MHz, DMSO-d6): δ (0.035 g, 52 %), mp. 167 – 170 °C, *α+D = –21.7 (c 0.75,
8.77 (d, J = 2.4 Hz, 1H), 8.52 (dd, J = 8.5 Hz, 2.4 Hz, 1H), 7.80 (d, MeOH). IR (KBr): 3401, 2927, 1618, 1586, 1499, 1340, 1329,
J = 8.5 Hz, 1H), 5.70 (d, J = 5.3 Hz, 1H), 4.58 (d, J = 18.4 Hz, 1H), 1141, 1075, 891, 869, 820, 786, 728, 657 cm-1. H NMR (500
1
4.53 (d, J = 18.4 Hz, 1H), 4.17 – 4.23 (m, 1H), 1.27 (d, J = 6.9 Hz, MHz, DMSO-d6): δ 11.54 (bs, 1H), 8.21 (d, J = 2.1 Hz, 1H), 7.86
3H). 13C NMR (125 MHz, DMSO-d6): δ 209.3, 148.8, 146.6, (dd, J = 8.7 Hz, 2.1 Hz, 1H), 7.67 (d, J = 8.7 Hz, 1H), 6.45 (s, 1H),
137.7, 135.2, 127.5, 119.9, 72.4, 42.7, 19.5. HRMS–ESI+ (m / z, 5.52 (bs, 1H), 5.04 (q, J = 6.5 Hz, 1H), 1.50 (d, J = 6.5 Hz, 3H).
MeOH): calcd for C10H9N2O6 [M-H]-, 253.0461; found: 13C NMR (125 MHz, DMSO-d6): δ 149.7, 141.5, 131.9, 127.3,
253.0455.
120.4, 114.0, 104.8, 93.9, 60.7, 23.0. HRMS–EI (m / z): calcd for
C10H10N2O4 [M]+·, 222.0641; found: 222.0636.
Synthesis of (S)-1-(2,4-dinitrophenyl)-3-(tert-butyldiphenyl-
silyloxy)-butan-2-one (6l)
Notes and references
To solution of alcohol 5l (0.150 g; 0.59 mmol) in CH2Cl2 (1.3
mL), tert-butyl-diphenylsilyl chloride (0.240 g; 0.87 mmol) and
imidazole (0.070 g; 1.0 mmol) were added subsequently and
the mixture was stirred at room temperature for 1h. The
reaction mixture was diluted with CH2Cl2 (10 mL), washed with
water (5 mL), dried and evaporated. Crude product was
purified by column chromatography using hexane/CH2Cl2
mixure (2/1, next 1/1). 0.272 g (94 %) of pure product was
obtained. Colourless oil, *α+D22 = –50.5 (c 0.95, CHCl3). IR (film):
3073, 2958, 2932, 2859, 1726, 1606, 1537, 1472, 1427, 1346,
1
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