Synthesis of β-nitroamines using nanocrystalline MgO

Article abstract of DOI:10.1080/00397911003707147

Nanocrystalline magnesium oxide (NAP-MgO) was found to be an effective heterogeneous, solid base catalyst for the direct aza-Henry reaction of nitroalkanes and various N-arylidene-4-methylbenzenesulfonamides to afford the corresponding-nitroamines in exce

Full text of DOI:10.1080/00397911003707147

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Synthesis of β-Nitroamines Using
Nanocrystalline MgO
L. Chakrapani a & M. Lakshmi Kantam a
a Inorganic and Physical Chemistry Division, Indian Institute of
Chemical Technology, Hyderabad, India
Version of record first published: 04 Aug 2011.
To cite this article: L. Chakrapani & M. Lakshmi Kantam (2011): Synthesis of β-Nitroamines Using
Nanocrystalline MgO, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:23, 3442-3447
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Synthetic Communications1, 41: 3442–3447, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003707147
SYNTHESIS OF b-NITROAMINES USING
NANOCRYSTALLINE MgO
L. Chakrapani and M. Lakshmi Kantam
Inorganic and Physical Chemistry Division, Indian Institute of
Chemical Technology, Hyderabad, India
Abstract Nanocrystalline magnesium oxide (NAP-MgO) was found to be an effective
heterogeneous, solid base catalyst for the direct aza-Henry reaction of nitroalkanes and
various N-arylidene-4-methylbenzenesulfonamides to afford the corresponding b-nitro-
amines in excellent yields under mild conditions. The catalyst was recovered by simple cen-
trifugation and reused for three cycles with consistent activity.
Keywords Aza-Henry reaction; heterogeneous; NAP-MgO; b-nitroamines; solid base
INTRODUCTION
Construction of carbon–carbon bonds are important reactions that find numer-
ous applications in synthetic organic chemistry. b-Nitroamines are valuable synthetic
intermediates for the synthesis of a-amino acids and 1,2-diamines.[1] The aza-Henry
reaction (nitro-Mannich reaction) provides a valuable method for the synthesis of
b-nitroamines through the nucleophilic addition of nitroalkanes to imines.[2] Adams
et al. reported the Brønsted acid–catalyzed aza-Henry reaction of alkyl nitronate
anions and N-(4-methoxybenzyl) imine (PMB imine).[3] They also reported scandium
triflate–catalyzed addition reaction of 1-trimethylsilyl nitropropanate and PMB
imine.[4] The first direct asymmetric aza-Henry reaction of N-phosphinylimines with
nitromethane was developed by Yamada et al.[5] Later, several methods were
developed for the direct aza-Henry reaction of various electron-deficient imines,
carrying imine-activating groups such as N-phosphinoyl imine, a-iminoester, and
Received November 14, 2009.
Address correspondence to M. Lakshmi Kantam, Inorganic and Physical Chemistry Division,
Indian Institute of Chemical Technology, Hyderabad 500 007, India. E-mail: mlakshmi@iict.res.in
3442

SYNTHESIS OF b-NITROAMINES
3443
Scheme 1. Direct aza-Henry reaction using NAP-MgO.
N-Boc imines.[6] However, the aza-Henry reaction of more available and stable
N-tosyl imine was less explored. Knudsen et al. reported the first aza-Henry reaction
of sulfonylimines with nitromethane using Yb(OiPr)3 as a catalyst.[7] Later, Qian et al.
reported the asymmetric version of this reaction using binuclear zinc complex with a
chiral semi-aza-crown ligand.[8] The toluene-sulfonyl activating group of imine can be
removed easily by treatment with Mg=MeOH,[9] treatment with phenol in refluxing
HBr=HOAc solution with addition of water,[10] or treatment with SmI2 in tetrahydro-
furan (THF) at room temperature to obtain b-nitroamines.[11]
Most of the methodologies are homogeneous in nature, where recyclability of
the catalyst could not be achieved. Heterogeneous catalysis is particularly attractive
as it allows the production and ready separation of large quantities of products with
the use of small amount of catalyst. In this direction, Kim et al.[12] reported the chiral
bis(oxazoline) ligand immobilized on mesoporous silica (SAB-15) for the asymmetric
aza-Henry reaction of N-protected a-iminoesters and nitroalkanes. We herein report
the use of a truly heterogeneous catalyst nanocrystalline magnesium oxide
(NAP-MgO) for the synthesis of b-nitroamines in excellent yields under mild
conditions (Scheme 1).
Recently, our group reported the synthesis of chiral epoxy ketones,[13] chiral nitro
alcohols and Michael adducts,[14] chiral b-hydroxy carbonyl compounds,[15] b-hydroxy-
a-diazo esters,[16] and a,b-unsaturated esters and nitriles by using NAP-MgO.[17]
Various magnesium oxide crystals [commercial MgO, CM-MgO (30 m2=g);
conventionally prepared MgO, NA-MgO (252 m2=g); aero-gel-prepared NAP-
MgO (590 m2=g)] were initially screened in the reaction of N-(4-chlorobenzylidene)-
4-methylbenzenesulfonamide with nitromethane at room temperature. NAP-MgO
was found to be more active when compared to the other crystalline forms of
MgO (Table 1).
Table 1. Direct aza-Henry reaction of N-(4-chlorobenzylidene)-4-methyl-benzenesulfonamide and
nitromethane at room temperature catalyzed by different crystallites of MgOa
Entry
Catalyst
Solvent
Time (min)
Yieldb (%)
1
2
3
NAP-MgO
CP-MgO
CM-MgO
DMF
DMF
DMF
05
15
60
98
92
89
aConditions: catalyst (10 mg), N-(4-chlorobenzylidene)-4-methylbenzene-sulfonamide (0.25 mmol),
nitromethane (10 equiv.).
bIsolated yields.

3444
L. CHAKRAPANI AND M. LAKSHMI KANTAM
Table 2. Screening of solvents in the reaction of N-(4-chlorobenzylidene)-4-methylbenzenesulfonamide
and nitromethane using NAP-MgO at room temperaturea
Entry
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
DMF
MeOH
THF
5
180
180
360
360
360
92
76
59
54
10
05
MeCN
DCM
Toluene
aConditions: NAP-MgO (10 mg), N-(4-chlorobenzylidene)-4-methyl-benzenesulfonamide (0.25 mmol),
nitromethane (10 equiv.), solvent (2 mL).
bIsolated yield.
RESULTS AND DISCUSSION
In the process of optimizing the reaction conditions, we studied the aza-Henry
reaction of N-(4-chlorobenzylidine)-4-methylbenzenesulfonamide with nitromethane
in the presence of NAP-MgO with different solvents; dimethylformamide (DMF),
Table 3. Direct aza-Henry reaction of various N-arylidene-4-methylbenzene sulfonamides and nitro-
alkanes using NAP-MgOa
Entry
Ar
R0
Time (min)
Yieldb (%)
1
2
3
4
5
4-No2-C6H4
4-Cl-C6H4
4-OMe-C6H4
C6H5
H
H
H
H
H
5
5
96
98, 96c
90
20
15
5
93
96
4-CF3-C6H4
6
H
15
95
7
8
1
CH3
C2H5
CH3
15
15
15
15
15
15
96
96
97
98
93
95
1
9
4-Cl-C6H4
4-Cl-C6H4
C6H5
10
11
12
C2H5
CH3
C2H5
C6H5
aConditions: Catalyst (10 mg), N-arylidene-4-methylbenzene sulfonamide (0.25 mmol), nitroalkane (10
equiv.), DMF (2 mL).
bIsolated yields.
cYield after third cycle.

SYNTHESIS OF b-NITROAMINES
3445
MeOH, THF, MeCN, dichloromethane (DCM), and toluene. Among these solvents,
the rate of the reaction was very fast in DMF, and the corresponding b-nitroamine
was obtained in excellent yields. Only a trace of the product was obtained in the non-
polar solvent, toluene and DCM (Table 2).
A variety of different N-benzylidine-4-methylbenzenesulfonamides, containing
electron-withdrawing or donating groups, and heterocyclic aldimines were subjected
to react with nitromethane to afford the corresponding b-nitroamines in excellent
yields (Table 3). Later, the reaction was carried out with other nitroalkanes, such
as nitroethane and 1-nitropropane. The reactions proceeded well to afford the
corresponding b-nitroamines with 1:1 diastereoselectivity in excellent yields.
After completion of the reaction [monitored by thin-layer chromatography
(TLC)], the reaction mixture was centrifuged to separate the catalyst, washed several
times with ethyl acetate and ether, and air dried. The recovered catalyst was recycled
three times without loss of activity after activation at 250 ꢀC for 1 h under a flow of
nitrogen.
CONCLUSION
In conclusion, we have shown that NAP-MgO is a highly active, reusable cata-
lyst for the synthesis of b-nitroamines. Thus nanocrystalline MgO, with its definite
shape, size, and accessible OH groups, and higher density of Mgþ at the edges=
corners, shows high activity in the synthesis of b-nitroamines.
EXPERIMENTAL
Typical Experimental Procedure for the Synthesis of b-nitroamines
DMF (2 mL) was added to a dried 25-mL round-bottomed flask charged with
NAP-MgO (10 mg) followed by nitroalkane (10 equiv.) and N-arylidine-4-methylben-
zenesulfonamide (0.25 mmol) at room temperature. The reaction was monitored by
TLC. After completion of the reaction, the catalyst was separated by centrifuging the
reaction mixture, and the supernatant solution was quenched with saturated sodium
chloride solution and extracted with ethyl acetate. The organic layer was dried over
anhydrous Na2SO4 and concentrated to afford the crude product. Column chromato-
graphy of the crude on silica gel (60–120 mesh) using a mixture of ethyl acetate and hex-
ane in varying proportions as eluent, gave the corresponding aza-Henry adduct. All the
1
new compounds are characterized by H NMR, electrospray ionization–mass spec-
trometry (ESI-MS), and high resolution mass spectrometry (HRMS).
Selected Data
Entry 7, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 1.3 (d, 3H,
J ¼ 6.0), 2.36 (s, 3H), 4.8 (m, 2H), 6.0 (s, 2H), 7.1 (m, 2H), 7.4 (d, 2H, J ¼ 7.5),
8.5 (d, 1H, J ¼ 8.3 Hz); mass (ESI): m=z 347 (M þ Naþ); Anal. calcd. for
C14H16N2O5NaS: 347.0677; found: 347.0667.
Entry 8, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 0.8 (m, 3H), 2.3 (s,
3H), 4.7 (m, 2H), 6.0 (s, 2H), 7.0 (m, 3H), 7.4 (d, 2H, J ¼ 7.9), 8.5 (d, 1H, J ¼ 9.5);

3446
L. CHAKRAPANI AND M. LAKSHMI KANTAM
mass (ESI): m=z 361 (M þ Naþ); anal. calcd. for C15H18N2O5NaS: 361.0834; found:
361.0844.
Entry 9, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 1.2 (d, 3H, J ¼
6.8), 2.3 (s, 3H), 4.6 (m, 2H), 6.7 (m, 6H), 7.3 (d, 2H, J ¼ 8.3), 8.5 (d, 1H,
J ¼ 9.0); mass (ESI): m=z 391 (M þ Naþ); anal. calcd. for C16H17N2O4NaSCl:
391.0495; found: 391.0483.
Entry 10, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 0.8 (m, 3H,
J ¼ 6.8), 1.2 (m, 2H), 2.3 (s, 3H), 4.6 (m, 2H), 6.9 (m, 6H), 7.3 (d, 2H, J ¼ 8.3),
8.5 (d, 1H, J ¼ 9.1); mass (ESI): m=z 405 (M þ Naþ); anal. calcd. for C17H19N2O4-
NaSCl: 405.0651; found: 405.0671.
Entry 11, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 1.2 (m, 3H), 2.3
(s, 3H), 4.6 (m, 2H), 6.9 (d, 2H, J ¼ 8.4), 7.1 (m, 5H), 7.3 (d, 2H, J ¼ 8.4), 8.5 (d, 1H,
J ¼ 9.8); mass (ESI): m=z 357 (M þ Naþ); anal. calcd. for C16H18N2O4NaS:
357.0884; found: 357.0870.
Entry 12, Table 3. 1H NMR (200 MHz, CDCl3 þ DMSO) d 0.7 (m, 3H), 1.2
(m, 2H), 2.2 (s, 3H), 4.5 (m, 2H), 6.8 (d, 2H, J ¼ 8.3), 7.0 (m, 5H), 7.2 (d, 2H,
J ¼ 8.3), 8.5 (d, 1H, J ¼ 9.7); mass (ESI): m=z 371 (M þ Naþ); anal. calcd. for
C17H20N2O4NaS: 371.1041; found: 371.1038.
ACKNOWLEDGMENTS
We thank the Council of Scientific and Industrial Research (CSIR) for finan-
cial support under the Task Force Project CMM-0005. L. C. P. thanks the CSIR,
India, for providing a senior research fellowship.
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