Bis(dealkoxycarbonylation) of nitroarylmalonates: A facile entry to alkylated nitroaromatics

Article abstract of DOI:10.1055/s-2000-8209

A simple approach to alkylated nitroaromatics from substituted nitroaryl malonic esters by double decarboxylation is detailed.

Full text of DOI:10.1055/s-2000-8209

SHORT PAPER
1659
Bis(dealkoxycarbonylation) of Nitroarylmalonates: A Facile Entry to
Alkylated Nitroaromatics
Mukund Gurjar,* Dandepally Srinivasa Reddy, Andappan Murugaiah, Subbaiah Murugaiah
National Chemical Laboratory, Pune-411 008, India
E-mail: gurjar@dalton.ncl.res.in
Received 15 May 2000; revised 27 June 2000
Abstract: A simple approach to alkylated nitroaromatics from sub-
stituted nitroaryl malonic esters by double decarboxylation is de-
tailed.
Key words: nucleophilic aromatic substitutions, Krapcho’s decar-
boxylation, alkylations, nitrotoluene, arenes
Scheme 1
Introduction of alkyl groups in aromatic rings is an impor-
tant step in organic synthesis. The conventional Friedel
Crafts alkylation,1 alkyation of metallated arenes, particu-
larly in the presence of directed metallating groups (ortho
effect),2 nucleophilic addition to arene-transition metal
carbonyl complexes,3 transition metal catalysed nucleo-
philic substitution of aryl halides,4 aromatic substitution
via nucelophilic addition to electron deficient arenes (in-
cluding vicarious and ipso)5 and olefin insertion via C-H
activation6 are some of the elegant methods to realise the
phenomenon. Hoz et al.7 have recently demonstrated the
application of trialkyboranes in base-promoted alkylation
of nitroaromatics.
To elaborate the scope of this investigation, different dis-
ubstituted malonic esters (Table, Entries 8 11) were pre-
pared from halonitrobenzenes and monoalkyl malonic
esters. Exposure of these compounds to the similar condi-
tions described above, enabled to access various alkyl ni-
trobenzenes (Table, Entries 8 11).
The proposed mechanism involves two stages: initial de-
carboxylation of malonate via competitive BAC2 or BAL2
pahtway8 to give o-nitrophenyl acetate which then under-
goes further decarboxylation to give o-nitrotoluene. Since
simple aryl malonic esters (without electron-withdrawing
NO2 group) stops at first decarboxylation itself, a ratio-
nale can be suggested that the second decarboxylation in
the case of nitroaryl-malonic esters becomes viable be-
cause of mesomeric stabilisation of benzylic anion by ni-
tro group at o/p position (Scheme 2).
Decarboxylation of aryl substituted malonic esters under
Krapcho’s conditions are known to provide aryl acetic es-
ters in good yield.8 However, to the best of our knowl-
edge, bis(decarboxylation) of arylmalonic esters has not
been reported. In continuation of our ongoing program to
synthesise medicinally important oxindole derivatives,
we observed by serendipity the complete decarboxylation
of nitroaryl malonates under Krapcho’s procedure. This
observation has been exploited to synthesise alkyl nitroar-
omatics which otherwise need number of steps.
For example, o-chloro/o-fluoronitrobenzene was convert-
ed to nitrophenyl malonic ester which on exposure to
NaCl in wet DMSO at 160 170 °C for 24 hours gave
o-nitrotoluene in 55% yield (Scheme 1). Encouraged with
this, various nitroaryl malonic esters were prepared from
the corresponding halonitrobenzenes by a modified pro-
cedure.9 Nitrohaloaromatic compounds were treated with
sodium salt of diethyl malonate in DMF at ambient tem-
perature to provide the corresponding diethyl (nitrophe-
nyl)malonates in good yields (Table). These compounds
were subjected to Krapcho’s reaction (NaCl, DMSO,
H2O, 160 170 °C) to afford the nitrotoluenes (Table, En-
tries 1 4 and 6) and nitroxylenes (Table, Entries 5 and 7).
Overall improved yields with shorter reaction timings
were observed when modified Krapcho’s condition i.e.
dibasic salt MgCl2•6H2O in dimethyl acetamide at 140
150 °C was employed.10
Scheme 2
In conclusion, we have developed a mild and efficient
procedure for alkylated aromatics which otherwise are
difficult to prepare, starting from halonitrobenzenes.
Needless to mention that the nitro group present in these
products can be a surrogate for introducing a variety of
functionalities in the aromatic ring.
Synthesis 2000, No. 12, 1659–1661 ISSN 0039-7881 © Thieme Stuttgart · New York

1660
M. Gurjar et al.
Table Synthesis of Alkylnitrobenzenesa,b
SHORT PAPER
a Conditions: A: NaCl/DMSO/H2O, 160 170 °C; B: MgCl2•6H2O/DMA, reflux.
b All the known compounds were identified by comparison with authentic samples. The products shown
under Entries 1-3, 5 and 6 are commercially available from Sigma-Aldrich Corporation/Lancaster Syn-
thesis L, while those under Entries 4 are reported in Dictionary of Organic Compounds, 1996, 3, 2073. 5-
Chloro-2,4-dimethylnitrobenzene (Entry 7) is reported in Dictionary of Organic Compounds, 1996, 2,
1335 (see also Experimental).
Synthesis 2000, No. 12, 1659–1661 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Bis(dealkoxycarbonylation) of Nitroarylmalonates: A Facile Entry to Alkylated Nitroaromatics
1661
Starting materials and reagents were purchased from Aldrich, Fluka
or Lancaster and used as received. TLC was performed on pre-coat-
ed silica gel plates (E-Merck, 60 F254) and visualized by UV irradi-
ation or spraying with anisaldehyde or phosphomolybdic acid stains
followed by heating. NMR spectra were recorded on Bruker spec-
trophotometers (AC 200, MSL 300) with TMS as an internal stan-
dard. IR spectra were obtained from Perkin-Elmer 16 PC- FTIR
spectrophotometer. EI Mass spectra were recorded on Finnigan
MAT-1020. Combustion data were recorded on Elmentar-Vario-EL
(Heraeus company Ltd. Germany).
Anal. calcd for C8H8ClNO2: C, 51.75; H, 4.31. Found: C, 51.85; H,
4.43.
2-Ethyl-4-methylnitrobenzene
1H NMR (200 MHz, CDCl3): = 1.28 (t, 3 H, J = 8.3 Hz), 2.41 (s,
3 H), 2.91 (q, 2 H, J = 8.3 Hz), 7.15 (m, 2 H), 7.82 (d, 1 H, J = 8.3
Hz).
13C NMR (75 MHz, CDCl3): = 14.9, 21.3, 26.3, 124.9, 127.3,
131.1, 139.1, 143.3.
1
IR (CHCl3): = 836, 1344, 1520, 1588, 2928 cm .
Bis(decarboxylation) of Nitroarylmalonates; General Proce-
dure
Anal. calcd for C9H11NO2: C, 65.44; H, 6.66; N, 8.48. Found: C,
65.20; H, 6.92; N, 8.40.
Condition A: A mixture of diethyl (halonitrophenyl)malonate
(5 mmol), NaCl (1.17 g, 20 mmol), and H2O (10 mmol) in DMSO
(20 mL) was heated at 160 170 °C (monitored by TLC). The mix-
ture was partitioned between Et2O (50 mL) and H2O (50 mL), the
Et2O was dried (Na2SO4) and concentrated to afford the residue
which was chromatographically purified on silica gel to afford the
pure product (Table).
2-(But-3-enyl)-5-chloronitrobenzene
1H NMR (200 MHz, CDCl3): = 2.38 (q, 2 H, J = 8.2 Hz), 2.96 (t,
2 H, J = 8.2 Hz), 5.05 (m, 2 H), 5.79 (m, 1 H), 7.29 (d, 1 H, J = 9.6
Hz), 7.45 (d, 1 H, J = 9.6 Hz), 7.9 0 (s, 1 H).
13C NMR (75 MHz, CDCl3): = 31.9, 34.3 116.1, 124.6, 132.7,
133.0, 136.5, 149.6.
Condition B: A mixture of diethyl (halonitrophenyl)malonate
(5 mmol) and MgCl2•6H2O (3.11 g, 10 mmol) in dimethyl aceta-
mide (10 mL) was heated at 140 150 °C (monitored by TLC). The
mixture was worked up as described above to provide the pure prod-
uct (Table).
1
IR (CHCl3): = 1278, 1350, 1530, 3080 cm .
Anal. calcd for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62, found: C,
56.62; H, 4.47; N, 6.82.
Acknowledgement
5-Chloro-2,4-dimethylnitrobenzene
1H NMR (200 MHz, CDCl3): = 2.45 (s, 3 H), 2.60 (s, 3 H), 7.20
(s,1 H), 8.05 (s, 1 H).
The authors DPSR and AMSM thank Council of Scientific and In-
dustrial Research, New Delhi for award of a fellowship.
13C NMR (75 MHz, CDCl3): = 19.5, 19.7, 124.67, 131.8, 134.5,
141.8, 146.6.
References
1
IR (CHCl3): = 764, 1364,1568 cm .
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1
IR (CHCl3): = 760, 1344, 1522, 1768 cm .
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1
IR (CHCl3): = 890, 1124, 1348, 1520, 2974 cm .
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2 H, J = 8.5 Hz), 7.32 (d, 1 H, J = 10.1 Hz), 7.48 (dd, 1 H, J = 2.3,
10.5 Hz), 7.85 (s, 1 H).
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138.0.
1
IR (CHCl3): = 760, 764, 1120, 1354, 1530 cm .
EI-MS: m/z: 185 (M+).
Article Identifier:
1437-210X,E;2000,0,12,1659,1661,ftx,en;Z04200SS.pdf
Synthesis 2000, No. 12, 1659–1661 ISSN 0039-7881 © Thieme Stuttgart · New York