Henry and Mannich reactions of polynitroalkanes in ionic liquids

Article abstract of DOI:10.1016/j.mencom.2011.01.009

Based on Henry and Mannich reactions of polynitroalkanes for the first time implemented in ionic liquids, ecologically pure and safe methods for the synthesis of polynitro alcohols and N-2,2,2-trinitroethyl derivatives of low basic amino compounds (urea, acetamide, 4-amino-3-methylfuroxan) have been elaborated.

Full text of DOI:10.1016/j.mencom.2011.01.009

Mendeleev
Communications
Mendeleev Commun., 2011, 21, 21–23
Henry and Mannich reactions of polynitroalkanes in ionic liquids
Margarita A. Epishina, Igor V. Ovchinnikov, Alexander S. Kulikov,
Nina N. Makhova* and Vladimir A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: mnn@ioc.ac.ru
DOI: 10.1016/j.mencom.2011.01.009
Based on Henry and Mannich reactions of polynitroalkanes for the first time implemented in ionic liquids, ecologically pure and safe
methods for the synthesis of polynitro alcohols and N-2,2,2-trinitroethyl derivatives of low basic amino compounds (urea, acetamide,
4-amino-3-methylfuroxan) have been elaborated.
Ionic liquids (ILs) represent one point of ‘green chemistry’,
since they are non-flammable, non-volatile, can be regenerated
and reused repeatedly.1–5 Moreover, being highly polar com-
pounds, ILs accelerate diverse heterolytic processes, including
reactions of CH-acids and 1,3-dipoles.6–9 Examples of Henry
and Mannich reactions in ILs deal mostly with addition of carbonyl
compounds to CH-acids containing a nitrile or alkoxycarbonyl
group as the activating substituent.10–13 Data on reaction of nitro
compounds in ILs are scarce: primary mononitroalkanes were
involved in the Henry reaction14–16 and in a three-component
Mannich condensation.17 ILs have not hitherto been used in
reactions of polynitroalkanes.
In this work we report on the application of ILs as reaction
media and catalysts in syntheses of polynitroalcohols [2,2,2-tri-
nitroethanol (TNE) and 2,2-dinitropropane-1,3-diol] and trinitro-
ethylamino compounds based on Henry and Mannich reac-
tions. TNE is the starting compound in syntheses of energy-rich
materials such as N,N'-bis(2,2,2-trinitroethyl)urea,18 N,N'-bis-
(2,2,2-trinitroethyl)ethylenedinitramine,19 tetrakis(2,2,2-trinitro-
ethyl)orthocarbonate (TNEOC) oxidant.20 A known method for
TNE synthesis involves heating of equimolar amounts of nitroform
and paraformaldehyde in CCl4 at 60–65°C.21
In our experiments for the preparation of TNE, we studied the
effect of the IL anion and cation {1-butyl-3-methylimidazolium
tetrafluoroborate (hexafluorophosphate) [bmim][BF4]([PF6]) and
1-ethyl-3-methylimidazolium hydrogensulfate [emim][HSO4]}
on the reaction between trinitromethane and paraformaldehyde
(with a small excess of trinitromethane) (Scheme 1).† The highest
yield (89%) was achieved when the reaction was carried out in
[emim][HSO4] at 20°C for 24 h (Table 1, entry 3). The yield of
TNE under the same conditions was 50% in [bmim][PF6] and
81% in [bmim][BF4]. After extraction of TNE with tert-butyl
methyl ether from [emim][HSO4], the IL was reused providing
to similar yields; the yield of TNE after water treatment followed
by extraction with ButOMe in the fourth experiment was 94%
(Table 1, entry 3). Evidently, TNE was extracted incompletely in
the previous experiments. It is important that, unlike in the known
method,21 extraction from the IL followed by solvent evaporation
in vacuo gives crystalline TNE with mp 70–72°C, as that of the
analytically pure specimen.21
Table 1 Synthesis of TNE in ILs.
Entry
IL
Yield of TNE (%) (cycle)
1
2
3
[bmim][BF4]
[bmim][PF6]
[emim][HSO4]
80
50
89 (1), 86 (2), 83 (3), 94 (4)
The similar technique was used for the synthesis of 2,2-di-
nitropropane-1,3-diol (DNPD)‡ from paraformaldehyde and dinitro-
methane generated from dinitromethane sodium salt by treat-
ment with various acids (HCl, CF3COOH, AcOH) [molar ratio
CH2O:NaCH(NO2)2:acid = 2.2:1.0:1.0]. In this case, the ILs,
the reaction temperature and time were also varied. A rather
satisfactory procedure comprised the reaction in [bmim][BF4]
at 1–3°C using an equimolar amount of AcOH with respect to
NaCH(NO2)2; however, the yield of DNPD even under these
conditions was as low as 40%, which was lower than the 66%
yield in water.22
Further we studied the reaction of TNE with poorly basic
amino compounds such as urea 1 (pKa 0.123), acetamide 2
(pKa –0.423) and 4-amino-3-methylfuroxan 3 (pKa –3.0124) in
‘acidic’ IL [emim][HSO4]. The synthesis of 1,3-bis(2,2,2-trinitro-
ethyl)urea 4 was carried out at 20°C without a catalyst or in the
presence of a catalytic amount of H2SO4. Three procedures were
used for this purpose (Scheme 2, Table 2): (1) simultaneous
†
IR spectra were measured on a Specord-M82 spectrometer. NMR
spectra were recorded using a Bruker AM-300 spectrometer (300 for 1H,
75.47 for 13C and 21.69 MHz for 15N). TMS was used as the internal
standard in H and 13C spectra and MeNO2 as the external standard in
1
14N NMR spectra. TLC was performed on silica gel plates (Silufol UV-254).
4-Amino-3-methylfuroxan was synthesized according to a procedure
reported elsewhere.26
2,2,2-Trinitroethanol (TNE). The mixture of trinitromethane (0.36 g,
2.4 mmol) and paraformaldehyde (0.06 g, 2 mmol) was stirred in 1 g of
[emim][HSO4] for 24 h at 20°C. 2,2,2-Trinitroethanol was extracted with
ButOMe (3×3 ml). The extract was washed with water (5×3 ml) and dried
with MgSO4; the solvent was evaporated in vacuo. Yield 0.32 g (89%),
mp 71–72°C (ButOMe) (lit.,21 mp 72°C). 1H NMR (CD3CN) d: 4.0 (br.s,
1H, OH), 4.95 (s, 2H, CH2). 13C NMR (CD3CN) d: 63.5 (CH2), 127.5
[C(NO2)2]. 14N NMR (CD3CN) d: –30.35 (NO2). The IL was evaporated
in vacuo with heating and used for the three syntheses. Reaction mixture
of the fourth synthesis after the reaction completion was treated with
water (3 ml) followed by extraction with ButOMe.
i
HC(NO2)3 + CH2O
(NO2)3CCH2OH
TNE (89–94%)
‡
2,2-Dinitropropane-1,3-diol (DNPD). Yield 40%, mp 141–142°C
(ButOMe) (lit.,22 mp 142°C). 1H NMR (CD3CN) d: 3.9 (br.s, 2H, OH),
4.44 (s, 4H, CH2). 13C NMR (CD3CN) d: 61.15 (CH2), 119.4 [C(NO2)3].
14N NMR (CD3CN) d: –12.04 (NO2).
Scheme 1 Reagents and conditions: i, CH2O (1.0 mmol), CH(NO2)3
(1.2 mmol), IL (1 g), 20°C, 24 h.
© 2011 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2011, 21, 21–23
CH2O
ii
MeCONH2
[ MeCONHCH2OH ]
NH2CONH2
[ HOCH2NHCONHCH2OH ]
[bmim][X]
K2CO3
CH2O
2
7
1
5
CH2O
HC(NO2)3
X = BF4, PF6
i or iv*
iv (O2N)3CCH2OH
iii HC(NO2)3
HC(NO2)3
MeCONHCH2C(NO2)3
6 (75–81%)
(O2N)3CCH2NHC(O)NHCH2C(NO2)3
4
Scheme 3
Scheme 2 Reagents and conditions: i, [emim][HSO4], cat. H2SO4, 20°C,
48 h; ii, [emim][HSO4], 50°C, 0.4 h; iii, [emim][HSO4], cat. H2SO4, 20°C,
24 h; iv*, [emim][HSO4], CH2O + CH(NO2)3, then 1; iv, [emim][HSO4],
20°C, 48 h.
K2CO3, while the entire process took 24 h at 20°C. The yield and
quality of the final product were not essentially dependent on
the IL used; IL could be recycled at least three times without a
considerable decrease in the yield.
Table 2 Synthesis of 1,3-bis(2,2,2-trinitroethyl)urea 4 in [emim][HSO4].
Similarly, 3-methyl-4-(2,2,2-trinitroethyl)aminofuroxan 9†† was
obtained in 37% yield in [bmim][BF4] (Scheme 4) through the
preliminary in situ obtaining N-hydroxymethyl derivative 8 from
4-amino-3-methylfuroxan 3 and paraformaldehyde. The attempted
reactions of acetamide 2 and aminofuroxan 3 with TNE in ILs
failed to produce the corresponding Mannich products 6 and 9.
Entry Method IL/g
T/°C Time/h Yield (%) (cycle)
1
2
3
i
i
2.0 + H2SO4 50
(7 drops)
24
48
Decomp.
3.5 + H2SO4 20
(7 drops)
60
60
ii
3.5 + H2SO4 50
0.4
24
iii
(7 drops)
20
20
20
Me
NH2
Me
NHCH2OH
4
5
6
iv*
iv
3.5
24
24
24
52
36
77
CH2O
3.5
[bmim][BF4]
K2CO3
N
N
N
N
O
O
iv
3.5 + H2SO4 20
(7 drops)
O
O
3
8
7
iv
3.5
20
48
90 (1), 86 (2), 84 (3), 88 (4)
Me
NHCH2C(NO2)3
mixing of three components, viz. urea 1, paraformaldehyde and
trinitromethane (pathway i, entries 1, 2), (2) reaction of pre-
synthesised in situ 1,3-bis(hydroxymethyl)urea 5 with trinitro-
methane (pathways ii, iii, entry 3) and (3) condensation of urea
1 with TNE (pathway iv, entries 4–7), including preliminary
one-pot preparation of the latter in an IL without isolation in
pure form followed by addition of urea (entry 4). The target
product 4 was formed in all the reactions, but the highest yield
(90%) was reached where the reaction of urea 1 with TNE was
carried out for 48 h in the absence of H2SO4 (Table 2, entry 7);
when the IL itself acted as a catalyst. In the optimum case, the IL
was recycled three times after extraction of the final product
without a considerable decrease in the product yield (Table 2,
entry 7). The product obtained had a high quality and did not
need additional purification.§
HC(NO2)3
N
N
O
O
9 (37%)
Scheme 4
It is evident that conditions for the formation of Mannich
products are largely determined by the basicity of the starting
aminocompound.Apparently,morebasicureacanbetransformed
into the product 4 by any of procedures (see Scheme 2), however,
the reaction with TNE was found to be the optimum one. As for
less basic amino compounds 2 and 3, the target products 6 and 9
can be accessed only after the preliminary synthesis of the cor-
responding N-hydroxymethyl derivatives.
The reaction of acetamide 2, paraformaldehyde and nitroform
(Scheme 3) was also performed in three ways in two different
ILs, viz. [bmim][BF4] and [bmim][PF6]; however, in this case
the highest yield 75–81% of N-(2,2,2-trinitroethyl)acetamide 6¶
was achieved when acetamide 2 was treated with paraformalde-
hyde to furnish in situ formed N-hydroxymethylacetamide 7,
which was then treated with nitroform. In this manner, the first
stage was carried out in the presence of a catalytic amount of
Previously,18 compound 4 was prepared by heating of urea,
paraformaldehyde and nitroform in molar ratio 1:2:2 in water
at 80°C followed by crystallization from aqueous EtOH in 62%
yield. Compound 6 was synthesized by reaction of N-hydroxy-
methylacetamide with nitroform,25 and although its yield (75%)
was comparable with that in ILs (75–81%), the conversional
means required heating (50–70°C).25 Mannich reaction of amino
furoxans with polynitroalkanes was not before studied.
Thus, Henry and Mannich reactions of polynitroalkanes have
been for the first time performed in ILs as reaction medium.
As exemplified on TNE, 1,3-bis(2,2,2-trinitroethyl)urea and
N-(2,2,2-trinitroethyl)acetamide, replacementoforganicsolvents
by ILs allowed one not only to raise yields of these compounds
and to provide their high quality, but also to improve appreciably
ecological characteristics and safety of these processes. The data
obtained can be extended on other polynitro compounds with
practically useful properties.
§
1,3-Bis(2,2,2-trinitroethyl)urea 4. The mixture of urea (0.06 g, 1 mmol)
and TNE (0.4 g, 2.2 mmol) in 3.5 g of [emim][HSO4] was stirred for 48 h
at 20°C. 1,3-Bis(2,2,2-trinitroethyl)urea was extracted with ButOMe (3×3ml).
The extract was washed with water (5×3 ml) and dried with MgSO4; the
solvent was evaporated in vacuo. Yield 0.35 g (90%), mp 170–171°C
(ButOMe) (lit.,18 mp 170–171°C). H NMR (CD3CN) d: 4.95 (d, 4H,
1
CH2, J 7 Hz), 6.16 (t, 2H, NH, J 7 Hz). 13C NMR (CD3CN) d: 44,60
(CH2), 117.0 [C(NO2)3], 156.25 (C=O). 14N NMR (CD3CN) d: –30.62
(NO2). The IL was evaporated in vacuo with heating and used for the next
synthesis.
3
3
†† 3-Methyl-4-(2,2,2-trinitroethyl)aminofuroxan 9.Yield 37%, mp 124–125°C.
1H NMR (acetone-d6) d: 2.15 (s, 3H, Me), 5.38 (d, 2H, CH2, 3J 7.0 Hz),
6.85 (t, 1H, NH, 3J 7.0 Hz). 13C NMR (acetone-d6) d: 5.94 (Me), 45.16 (CH2),
106.6 (C3 fur. ring), 125.40 [C(NO2)3], 156.40 (C4 fur. ring). 14N NMR
(acetone-d6) d: –30.68 (NO2). IR (n/cm–1): 3360, 3284 (NH), 3052, 3000,
2948 (CH), 1632 (fur. ring), 1528, 1336 (NO2), 1296, 1212, 1028, 808.
¶
N-(2,2,2-Trinitroethyl)acetamide 6. Yield 81%, mp 89–90°C (ButOMe)
(lit.,25 88–90°C). 1H NMR (DMSO-d6) d: 1.95 (s, 3H, Me), 5.07 (d, 2H,
CH2, J 6.5 Hz), 8.75 (t, 1H, NH, J 6.5 Hz). 13C NMR (DMSO-d6) d:
22.80 (Me), 63.23 (CH2), 126.00 [C(NO2)3], 173.60 (C=O). 14N NMR
(DMSO-d6) d: –31.98 (NO2). IR (n/cm–1): 3272 (NH), 3060, 3012, 2960
(CH), 1676 (C=O), 1588, 1360 (NO2), 1304, 1132, 1092, 808.
3
3
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Received: 2nd July 2010; Com. 10/3555
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