Transformations of nitrates (nitro esters) of amino alcohols involving both functions 1. Reaction with alkali metal hydrogen carbonates

Article abstract of DOI:10.1023/B:RUCB.0000011882.57315.97

The reaction of nitrates (nitro esters) of amino alcohols with alkali metal hydrogen carbonates yielding oxazohdin-2-ones and tetrahydro-1,3-oxazin-2-ones was discovered. A large number of both known and newly synthesized nitrates of amino alcohols with various structures were involved in this reaction, and the optimum reaction conditions were found. New oxazolidin-2-ones and tetrahydro-1,3-oxazin-2-ones were synthesized. Two more transformations were found for a few examples. One of the reactions gives nitramino alcohols, whereas another reaction affords polymers.

Full text of DOI:10.1023/B:RUCB.0000011882.57315.97

Russian Chemical Bulletin, International Edition, Vol. 52, No. 10, pp. 2221—2230, October, 2003
2221
Transformations of nitrates (nitro esters)
of amino alcohols involving both functions
1. Reaction with alkali metal hydrogen carbonates
A. G. Korepin,ꢀ P. V. Galkin, N. M. Glushakova, E. K. Perepelkina, M. V. Loginova, V. P. Lodygina,
Yu. A. Ol´khov, and L. T. Eremenko
Institute of Problems of Chemical Physics, Russian Academy of Sciences,
142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (096) 515 3588. Eꢀmail: sma@icp.ac.ru
The reaction of nitrates (nitro esters) of amino alcohols with alkali metal hydrogen carbonꢀ
ates yielding oxazolidinꢀ2ꢀones and tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀones was discovered. A large
number of both known and newly synthesized nitrates of amino alcohols with various strucꢀ
tures were involved in this reaction, and the optimum reaction conditions were found. New
oxazolidinꢀ2ꢀones and tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀones were synthesized. Two more transformaꢀ
tions were found for a few examples. One of the reactions gives nitramino alcohols, whereas
another reaction affords polymers.
Key words: amino alcohols, Nꢀacylation, Oꢀnitration, nitrates (nitro esters) of amino
alcohols, hydrogen carbonates, cyclization, oxazolidinꢀ2ꢀones, tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀones,
rearrangement, polymerization.
Nitro esters of amino alcohols,* which are generally
prepared as nitrates by nitration of amino alcohols, have
been studied primarily as energetic compounds.1—5 Data
on their chemical transformations or the use of these
compounds in organic synthesis are scarce. As examples
we refer to the reaction of diethanolamine dinitrate
with formaldehyde giving rise to methylenediamine,6
Nꢀnitrosation of nitrates of amino alcohols containing
the secondary amino group,4,7 and Nꢀacylation of aminoꢀ
ethanol nitrate.8 The latter reaction was used in one of
alternative procedures for the preparation of Nꢀ(2ꢀnitroxyꢀ
ethyl)nicotinamide (Nicorandil), which is a new highly
efficient cardiac drug.9 In the aboveꢀcited examples, the
reactions proceed with the involvement of only one of
two reaction centers of amino alcohol nitrates, viz., the
amino group.
In the monograph,10 it was hypothesized that nitrates
of amino alcohols, like other derivatives of amines conꢀ
taining polar substituents (halogen atom or sulfate group)
in the β position, can be subjected to cyclization involving
both reaction centers to form ethyleneimines. The auꢀ
thors of the monograph10 referred to the study of Japaꢀ
nese chemists11 who examined the relationship between
the reactivity of ephedrine derivatives and their threeꢀ
dimensional structures. However, in the cited study, we
found no data on cyclization of ephedrine nitrate. The
cyclization reaction described in this study deals with a
halogen derivative. Apparently, the idea suggested in the
monograph10 has not as yet been confirmed experiꢀ
mentally.
Therefore, to our knowledge, transformations of niꢀ
trates of amino alcohols involving the amino and nitrate
groups are unknown. In our opinion, the discovery and
study of these reactions may help in gaining a better inꢀ
sight into the nature of nitrates of amino alcohols and
provide an approach to new compounds possessing useful
properties.
When studying the behavior of one of the nitrates of
amino alcohols, which we synthesized with the aim of
searching for new compounds possessing cardiac activity,
we found three types of transformations (Scheme 1).
The transformation (a) afforded the oxazolidine ring
analogously to the transformation known for βꢀhaloꢀ
alkylamines12,13 (Scheme 2).
Apparently, the transformation (b) belongs to a previꢀ
ously unknown type of rearrangements of nitrates of amino
alcohols (if this reaction proceeds according to an inꢀ
tramolecular mechanism).
The transformation (c) is somewhat analogous to
quaternization polymerization of Nꢀ(2ꢀnitroxyethyl)nicoꢀ
tinamide described earlier14 (Scheme 3).
According to the results of thermomechanical specꢀ
troscopy, compound 4 is a polymer with an amorphousꢀ
crystalline topological structure. In the temperature range
* Hereinafter, nitrates of amino alcohols.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2104—2112, October, 2003.
1066ꢀ5285/03/5210ꢀ2221 $25.00 © 2003 Plenum Publishing Corporation

2222
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
Korepin et al.
Scheme 1
Scheme 2
Scheme 3
Scheme 1), and established the structures of their reacꢀ
tion products.
R =
, n = 7
Results and Discussion
a. 2 equiv. of KHCO3, H2O; b. 2 equiv. of KOH, PriOH, MeOH;
c. 1 equiv. of KOH, MeOH
We studied the reactions of nitrates of amino alcohols
with potassium and sodium carbonates using both known
and, predominantly, newly synthesized nitrates with difꢀ
ferent structures (Table 1). The differences in the moꢀ
lecular structures are associated with the position of the
nitroxy group with respect to the amine nitrogen atom
(β or γ), the number of nitroxy and amino groups, the
nature of the amino group (primary or secondary), and
the presence or absence of the third functional group
(amide group). Compounds containing the amide group
were synthesized not only with the aim of studying their
from –100 °C to 6 °C, compound 4 occurs in the crystalꢀ
line glassy state. As the temperature is increased to 6 °C,
the segmental mobility starts to freeze out. At 117 °C and
127 °C, crystal modifications with molecular weights of
macromolecules of about 1•103 and 4•103, respectively,
start to melt. The temperature of the onset of molecular
flux is 141 °C.
In the present study, we examined primarily transforꢀ
mations of type (a), carried out reactions (b) and (c) (see
Scheme 4
n = 2 (5a), 3 (5b)
Compound
R
n
2
3
2
Compound
n
2
3
2
m
0
0
7a
7b
7c
4ꢀO2NC6H4
4ꢀO2NC6H4
4ꢀAcNHC6H4
7e
7f
7g
R =4ꢀO2NC6H4 (6a), 4ꢀAcNHC6H4 (6b),
m = 0 (6d), 2 (6e)
(6c),
2
7d
2

Transformations of nitro esters of amino alcohols
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
2223
Table 1. Characteristics of nitrates of amino alcohols and amido amino alcohols
Comꢀ
pound
Found
Calculated
Molecular
formula
1H NMR (DMSOꢀd6),
IR,
ν/cm–1
(%)
N
δ (J/Hz)
C
H
1а
36.70 4.02 19.63
36.57 4.19 19.39
C11H15N5O9 3.25 (t, 2 H, CH2NH, J = 5.3);
3.51 (t, 2 H, NHCH2, J = 4.5);
3.63 (dt, 2 H, CONHCH2,
1635, 1275, 870, 850 (ONO2);
2885, 2795, 2745, 2430 (NH2+);
1380 (NO3–); 3385, 1670 sh,
JCH—CH ≅ JCH—NH ≅ 5.3);
4.86 (t, 2 H, CH2ONO2,
1540 (NHCO); 1515, 1345 (NO2);
2975, 2935, 2860, 1460,
J = 4.5); 8.12 (d, 2 H, CH,
1440, 1420 (CH2);
J = 9.7); 8.38 (d, 2 H, CH,
1595, 1480, 1420, 870, 720 (Ar)
J = 9.7); 8.90 (br.s, NH•HNO3);
9.03 (br.t, 1 H, CONH,
JNH—CH ≅ 5.3)
1b
1е
1f
38.55 4.56 18.42
38.40 4.57 18.66
C12H17N5O9 2.06 (m, 2 H, CH2CH2CH2);
3.00—3.33 (br.m, 4 H, CH2NH2+CH2);
3.60 (m, 2 H, CONHCH2); 4.60 (t,
2 H, CH2ONO2, J ≅ 6.3); 8.20 (m,
1621, 1276, 852 (ONO2);
3024, 2791 (NH2+);
1379 (NO3–); 3380, 1647,
1541 (NHCO); 1518,
4 H, CH, AB system, ∆ν ≅ 40);
1343 (NO2); 2943, 2860,
1441 (CH2); 1600, 1490,
870, 720 (Ar)
1640, 1280, 842 (ONO2); 3000,
2800, 1650 (NH2+); 1380 (NO3–);
3395, 3275, 1675, 1555,
1510 (NHCO); 2955, 2840,
1460, 1435 (CH2)
AB
8.70 (br.m, 2 H, NH.HNO3);
9.00 (br.t, 1 H, CONH, J ≅ 5.0)
C10H22N8O14 3.17 (br.t, 2 H, CH2NH, J ≅ 5.9);
3.43 (br.m, 2 H, NHCH2);
25.20 4.98 23.59
25.11 4.64 23.42
3.49 (br.m, 2 H, CONHCH2);
4.80 (br.t, 4 H, CH2ONO2, J = 4.3);
8.81 (br.s, 4 H, NH•HNO3);
9.00 (br.t, 2 H, CONH,
JNH—CH ≅ 5.9)
28.17 5.17 22.06
28.46 5.18 22.13
C12H26N8O14 2.05 (m, 4 H, CH2CH2CH2);
3.11 (br.m, 8 H, CH2NHCH2);
∼3.5 (m, 4 H, CONHCH2);
1635, 1278, 878 (ONO2); 2970
(NH2+); 1380 (NO3–); 3350,
1670, 1521 (NHCO); 2965,
2849 sh, 1436 sh (CH2)
4.58 (t, 4 H, CH2ONO2, J ≅ 6.0);
8.60 (br.m, 4 H, NH•HNO3);
8.93 (br.t, 2 H, CONH,
JNH—CH ≅ 5.7)
1g
1i
17.62 5.27 25.76
17.46 4.76 25.45
C4H13N5O9
—
1637, 1273, 859, 847, 751 (ONO2);
2937 (NH3+); 2791, 2739 (NH2+);
1384 (NO3–); 1474 (CH2)
1361 sh, 1618, 1281, 875 (ONO2);
3027, 2792, 2425 (NH2+);
1382 (NO3–); 2940, 2850 sh,
1474 sh (CH2)
24.19 4.87 21.50
24.49 5.14 21.42
C8H20N6O12 2.06 (m, 4 H, CH2CH2CH2);
3.13 (t, 4 H, CH2NH, J ≅ 7.0);
3.29 (s, 4 H, NHCH2CH2NH);
4.60 (t, 4 H, CH2ONO2, J ≅ 7.0);
8.87 (br.s, 4 H, NH•HNO3)
chemical properties but also for the purpose of using these
compounds for the preparation of potentially biologically
active compounds belonging to a series of amino amide
derivatives. It is known15 that many compounds belongꢀ
ing to amino amides, which can be represented as monoꢀ
acylated diamines, possess high biological, including carꢀ
diac, activities. However, amino amides containing
nitroxyalkyl substituents remained unknown.
The starting amino alcohols containing amide
groups (amido amino alcohols) were synthesized by
N´ꢀacylation of Nꢀ(2ꢀhydroxyethyl)ethylenediamine (5a)
and Nꢀ(3ꢀhydroxypropyl)ethylenediamine (5b) with
4ꢀnitrobenzoic (6a), 4ꢀacetamidobenzoic (6b), nicotinic
(6c), oxalic (6d), and succinic (6e) esters (Scheme 4,
Table 2).
Then alcohols 7a—g were nitrated with nitric acid. It
should be noted that the expected nitrates were prepared
from alcohols 7a,b,e,f in high yields (Scheme 5, Table 2),
whereas the reactions with alcohols 7c,d,g afforded mixꢀ
tures of products, from which we failed to isolate indiꢀ
vidual compounds.
Two more new nitrates 1g,i were synthesized by nitraꢀ
tion of the known amino alcohols, viz., the aboveꢀ
mentioned Nꢀ(2ꢀhydroxyethyl)ethylenediamine (5a)16

2224
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
Korepin et al.
Scheme 5
R =
, n = 2 (1a), 3 (1b)
n = 2 (1e), 3 (1f)
and N,N´ꢀbis(3ꢀhydroxypropyl)ethylenediamine (5d)17
(Scheme 6, Table 1).
The maximum yields of the products (85—90%) were
achieved under the following conditions: potassium (soꢀ
dium) hydrogen carbonate was used in an excess of
25—50% with respect to the amount corresponding to the
stoichiometric coefficients in the equations presented in
Scheme 7, the temperature of the reaction mixture was
40—70 °C, and the reaction time was 20—60 min. The
reaction can be carried out at room temperature if the
The nitrates presented in Table 1 and nitrates 1h,18
1j,1,19 1k,19 and 1l 4 described earlier were used in the
reactions with potassium (sodium) hydrogen carbonates
in an aqueous medium. In all cases, the corresponding
oxazolidinꢀ2ꢀones or tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀones were
prepared (Scheme 7, Table 3).
Table 2. Characteristics of amido amino alcohols
Comꢀ
pound
Found
Calculated
Molecular
formula
1H NMR (DMSOꢀd6),
δ (J/Hz)
IR,
ν/cm–1
(%)
N
C
H
7а
7b
7с
52.40 6.11 16.39
52.17 5.97 16.59
C11H15N3O4 2.60 (t, 2 H, CH2N, J = 5.5);
2.73 (t, 2 H, CH2N, J = 6.0);
3.38 (unresolv. m, 2 H, CH2NHCO);
3.45 (t, 2 H, CH2O, J ≅ 5.5);
3285, 1660, 1550 (NHCO); 3105
(NH); 2700 br, 1070 (OH,
C—OH); 1515, 1340 (NO2);
2930, 2855, 1445 (CH2); 1595,
1480, 1425, 840 (Ar)
3.50 (br.s, NH, OH); 8.07 (d, 2 H,
CH, J = 8.1); 8.30 (d, 2 H, CH,
J = 8.1); 8.79 (br.t, H,
NHCO, JNH—CH ≅ 5.0)
53.81 6.13 15.30
53.92 6.41 15.72
C12H17N3O4 1.58 (m, 2 H, CH2CH2CH2);
2.62 (t, 2 H, NHCH2, J ≅ 6.6);
2.70 (t, NHCH2, J ≅ 6.0);
3920, 1660, 1552 (NHCO);
3109 (NH); 3266, 1069 (OH,
C—OH); 1517, 1340 (NO2);
2901, 2852, 2821, 1436 (CH2);
3032, 1598, 1486, 862, 722 (Ar)
3.24—3.45 (m, CONHCH2,
NH, OH); 3.47 (t, 2 H, CH2OH,
J ≅ 6.0); 8.15 (m, 4 H, CH, AB,
∆ν ≅ 40); 8.74 (br.t,
AB
1 H, CONH, J ≅ 5.0)
C13H19N3O3 2.06 (s, 3 H, CH3CO); 2.55, 2.66
(t, 2 H each, CH2NH, J ≅ 6.0);
58.54 7.05 15.80
58.85 7.22 15.84
3245, 1670, 1635, 1525
(NHCO); 3305 (NH); 3305,
1065 (OH, C—OH); 2935,
2900, 2845, 2825, 1745,
1455 (CH2); 1610, 1595,
1455, 855, 695 (Ar)
3.20—3.40 (m, CONHCH2, NH);
3.43 (t, 2 H, CH2OH, J ≅ 6.0);
4.50 (br.s, 1 H, OH); 7.71 (m,
4 H, CH, AB, ∆ν ≅ 40);
AB
8.29 (br.t, 1 H, CONHCH2,
J ≅ 5.0); 10.15 (br.s, 1 H, CONHAr)
(to be continued)

Transformations of nitro esters of amino alcohols
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
2225
Table 2 (continued)
Comꢀ
pound
Found
Calculated
Molecular
formula
1H NMR (DMSOꢀd6),
δ (J/Hz)
IR,
ν/cm–1
(%)
N
C
H
7d
57.33 7.49 20.11
57.40 7.22 20.08
C10H15N3O2 2.61 (t, 2 H, NHCH2CH2OH,
J ≅ 5.6); 2.71 (t, 2 H, CH2NH,
3325, 1660, 1540 (NHCO):
3305 (NH); 1590, 1745, 1425,
705 (ring); 2935, 2850,
1440 (CH2)
J ≅ 6.0); 3.37 (dt, 2 H, CONHCH2,
JCH—CH ≅ JCH—NH ≅6.0); 3.46 (t,
2 H, CH2OH, J = 5.6); 4.34 (br.s,
1 H, OH); 7.47 (dd, 1 H, CH(5),
3
3JCH—CH ≅ 8.0; JCH—CH≅ 5.0);
8.17 (dt, 1 H, CH(4), 3JCH—CH
≅
4
4
8.0; JCH—CH ≅ JCH—CH ≅ 2.0);
8.61 (br.t, 1 H, CONH,
JNH—CH ≅ 6.0); 8.67 (dd, 1 H,
CH(6), 3JCH—CH ≅ 5.0; 4JCH—CH
2.0); 8.99 (d, 1 H, CH(2),
4JCH—CH ≅ 2.0)*
≅
7е
7f
45.44 8.68 21.49
45.79 8.45 21.36
C10H22N4O4 (DMFAꢀd7) 2.66 (t, 4 H, NHCH2,
3275, 1675, 1655, 1520
J = 5.3); 2.77 (t, 4 H, NHCH2,
J ≅ 5.7); 3.32 (dt, 4 H,
(NHCO); 3295 (NH); 3480,
3270, 1060 (OH, C—OH);
2930, 2904, 2835, 1470,
CONHCH2, JCH—CH ≅ JCH—NH
5.7); 3.5 (br.s, 4 H, NH, OH);
3.51 (t, 4 H, CH2O, J = 5.3);
≅
1455, 1440 (CH )
2
8.61 (br.t, NHCO, JCH—NH ≅ 5.7)
C12H26N4O4 1.50 (m, 4 H, CH2CH2CH2);
2.59 (m, 4 H, NHCH2); 2.65 (m,
4 H, NHCH2); 2.80—3.40 (m,
CONHCH2, NH, OH); 3.49
(t, 4 H, CH2OH, J ≅ 6.0);
49.60 8.97 19.00
49.64 9.02 19.30
3267, 1657, 1553 (NHCO);
3113 (NH); 3923, 1041
(OH, C—OH); 2948, 2887,
2825, 1484, 1442,
1370 (CH2)
8.54 (br.t, 2 H, CONH,
JCH—NH ≅ 5.0)
7g
49.42 8.83 19.49
49.64 9.02 19.30
C12H26N4O4 2.30 (s, 4 H, CH2CO); 2.50 (m,
8 H, CH2NH); 3.10 (unresolv. m,
4 H, CH2NHCO); 3.42 (t, 4 H,
CH2O, J ≅ 5.4); 3.5 (br.s, NH,
OH); 7.85 (br.t, 2 H, NHCO,
JNH—CH ≅ 5.8)
3250, 1650, 1615, 1555
(NHCO); 3190 (NH); 3250,
1055 (OH, C—OH)
* The signal for the proton of the NH group is not observed because of its broadening due to exchange.
Scheme 6
to 5%) hardly compensates for time losses (an increase in
the reaction time by several hours). The reactions with
alkali metal carbonates (Na2CO3 or K2CO3) afforded
products in somewhat lower yields.
The transformation, apparently, proceeds through
the nucleophilic displacement of the nitroxy group
by the anion of carbonic acid to form hydrogen carꢀ
bonate of amino alcohol (Scheme 8) followed by the
intramolecular nucleophilic attack of the nitrogen
atom of the amino group on the carbon atom of the
carbonate group. Elimination of the H2O molecule gives
rise to a new C—N bond resulting in cyclization of the
molecule.
starting nitrates of amino alcohols are waterꢀsoluble. Howꢀ
ever, a small increase in the yield of the products (up
In conclusion, it should be noted that the main reꢀ
sult of the present study is the discovery of the reacꢀ

2226
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
Korepin et al.
Scheme 7
R = 4ꢀO2NC6H4
1, 8: n = 2 (a, e, h, j); 3 (b, f, i, k)
Scheme 8
tion of nitrates of amino alcohols involving both reꢀ
action centers, which provides fresh insight into the
reactivities of these compounds. Another result of
our study is that a new procedure was developed for the
synthesis of oxazolidinꢀ2ꢀones and tetrahydroꢀ1,3ꢀoxazinꢀ
2ꢀones, which supplements the set of known methꢀ
ods.21,22,23 The new method can sometimes be a proceꢀ
dure of choice due to its simplicity and the fact that it
requires readily accessible starting compounds. In addiꢀ
tion, in some cases the new method has no alternatives
(for example, in the synthesis of compounds 8g and 8l;
see Scheme 7).
n = 1, 2

Transformations of nitro esters of amino alcohols
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
2227
Table 3. Characteristics of oxazolidinꢀ2ꢀones and tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀones
Comꢀ
pound
Found
Calculated
Molecular
formula
1H NMR (solvent),
IR,
ν/cm–1
(%)
N
δ (J/Hz)
C
H
8а
51.33 4.57 15.35
51.61 4.69 15.05
C12H13N3O5 (DMSOꢀd6) 3.40 (t, 2 H, CH2NCO,
J ≅ 5.6); 3.45—3.56 (dt, 2 H,
3330, 1655, 1555 (NHCO);
2995, 1606, 1490, 870 (Ar);
2935, 2860, 1455, 1445 (CH2);
1725, 1270, 1200, 1105 (C=O,
C—O, C—N);
NHCH2, JCH—CH ≅ JCH—NH ≅ 5.6);
3.65 (t, 2 H, NHCH2CH2O,
J ≅ 7.6); 4.28 (t, 2 H, CH2O,
J ≅ 7.6); 8.04 (d, 2 H, CHC,
1520, 1430 (NO2)
J = 8.5); 8.31 (d, 2 H, CHCNO2,
J = 8.5); 8.95 (br.t, 1 H,
CONH, JNH—CH ≅ 5.6)
8b
8е
53.16 4.97 13.96
53.24 5.15 14.33
C13H15N3O5 (DMSOꢀd6) 1.93 (m, 2 H,
CH2CH2CH2); 3.20—3.60 (m, 6 H,
NHCH2, 2 NCH2); 4.14 (t, 2 H,
CH2O, J ≅ 5.0); 8.20 (m, 4 H,
3316, 1644, 1552 (NHCO);
3048, 2295, 1598, 1490, 842
(Ar); 2960, 2925, 2855, 1455,
1440 (CH2); 1671, 1266,
1150 (C=O, C—O, C—N);
1517, 1343 (NO2)
CH, AB system, ∆ν ≅ 52);
AB
8.94 (br.t, 1 H, CONH,
JNH—CH ≅ 4.0)
45.66 5.64 17.79
45.86 5.77 17.83
C12H18N4O6 (DMFAꢀd7) 3.30—3.50 (m, 8 H,
NHCH2CH2N); 3.71 (t, 4 H, NCH2,
J = 7.8); 4.30 (t, 4 H, CH2O,
J = 7.8); 8.90 (br.t, 2 H, CONH,
J ≅ 5.0)
3335, 1655, 1505 (NHCO);
2915, 2870, 1435 (CH2); 1730,
1265, 1110 (C=O,
C—O, C—N)
8f
49.00 6.40 16.30
49.12 6.48 16.36
C14H22N4O6 (DMSOꢀd6) 1.91 (m, 4 H,
CH2CH2CH2); 3.24—3.36 (m, 12 H,
NCH2); 4.12 (t, 4 H, OCH2, J ≅ 5.0);
8.83 (br.t, 2 H, CONH, J ≅ 5.0)
3351, 1672, 1507, 1496 (NHCO);
2949, 2873 sh, 1444, 1437 (CH2);
1683, 1259, 1151 (C=O,
C—O, C—N)
2974, 2927, 1629 (NH3+); 1382
(NO3–); 1485, 1428 (CH2);
8g
28.64 6.13 20.05
28.44 6.20 19.90
C5H13N3O6
(DMSOꢀd6) 3.02, 3.41 (t, 2 H each,
NCH2CH2NH2, J ≅ 5.8); 3.55 (m, 2 H,
NCH2, BB´ portion of AA´BB´); 4.27 (m, 1734, 1269, 1148 (C=O,
2 H, CH2O, AA´ portion of AA´BB´);
7.98 (br.s, 5 H, NH2 HNO3•H2O)
C—O, C—N)
.
8ha
8i
48.05 6.17 13.78
48.00 6.04 13.99
C8H12N2O4
(DMSOꢀd6) 3.34 (s, 4 H, NCH2CH2N); 3007, 2943, 2908, 2855,
3.57 (t, 4 H, CH2NCO, J = 7.9);
4.23 (t, 4 H, CH2O, J = 7.9)
1491, 1449 (CH2); 1731, 1273,
1217, 1134, 1115 (C=O,
C—O, C—N)
52.42 6.90 12.20
52.62 7.07 12.27
C10H16N2O4 (CDCl3) 2.04 (m, 4 H, CH2CH2CH2);
3.46 (t, 4 H, NCH2, J ≅ 6.0);
2972, 2943, 2914 sh, 2861,
1488, 1445, 1434 (CH2); 1683,
1672, 1267, 1137, 1114 (C=O,
C—O, C—N)
3.58 (s, 4 H, NCH2CH2N);
4.25 (t, 4 H, OCH2, J ≅ 6.0)
8jb
8kc
8l
41.20 5.48 16.02
41.38 5.79 16.08
C3H5NO2
C4H7NO2
C5H8N2O5
(CDCl3) 3.65 (m, 2 H, NCH2,
BB´ portion of AA´BB´); 4.46 (m, 2 H,
OCH2, AA´ portion of AA´BB´);
6.77 (br.s, 1 H, CONH)
(CDCl3) 1.79 (m, 2 H, CH2CH2CH2);
3.18 (td, 2 H, CH2N, J ≅ 5.9,
JCH—NH ≅ 2.3); 4.10 (t, OCH2, J ≅ 5.9);
7.03 (br.m, 1 H, CONH)
(CDCl3) 3.56 (t, 2 H, NCH2CH2ONO2, (Film from acetone) 2995,
J ≅ 5.1); ∼3.63 (m, 2 H, NCH2, 2925, 1486, 1436 (CH2); 1749,
BB´ portion of AA´BB´); ∼4.30 (m, 2 H, 1202, 1119 (C=O, C—O,
3275 (NH); 2995, 2931, 2855,
1485, 1411 (CH2); 1729, 1254,
1084 (C=O, C—O, C—N)
47.35 6.87 13.64
47.52 6.97 13.85
3275 (NH); 2984, 2960, 2925,
2849, 1493, 1480, 1458, 1427
(CH2); 1689, 1296, 1121, 1077
(C=O, C—O, C—N)
33.98 4.37 15.84
34.10 4.58 15.90
OCH2, AA´ portion of AA´BB´);
C—N); 1630, 1281,
4.59 (t, 2 H, CH2ONO2, J ≅ 5.1)
849 (ONO2)
a See Ref. 20.
b See Ref. 12.
с See Ref. 21.

2228
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
Korepin et al.
with stirring and cooled. The reaction product was filtered off,
washed, and recrystallized.
Experimental
Nꢀ(5ꢀHydroxyꢀ3ꢀazoniapentyl)ꢀ4ꢀnitrobenzamide (7a). Reꢀ
agents and conditions: 5a (0.11 mol), 6a (0.10 mol), PriOH
(20 mL), 80—85 °C, 7 h. The yield was 76%, m.p. 132—134 °C.
After recrystallization from MeOH, m.p. 135—137 °C.
The 1H NMR spectra of compounds 1a,e, 7a,c,e,g, and
8a,e,h were recorded on an NMR spectrometer equipped with a
superconducting magnet (294 MHz); the instrument was develꢀ
oped and built at the Institute of Problems of Chemical Physics
in Chernogolovka of the Russian Academy of Sciences. The
1H NMR spectra of all other compounds were measured on a
Bruker DXPꢀ200 spectrometer. The IR spectra were recorded
on a Specord Mꢀ82 spectrophotometer in KBr pellets. The polyꢀ
merization product of compound 1a was analyzed on a UIPꢀ70
thermomechanical analyzer.24
Commercial amino alcohols, such as 5a,c, aminoethanol,
3ꢀaminopropanol, and diethanolamine, and esters 6a—e conꢀ
taining no less than 98% of the main compound were used as the
starting reagents. Amino alcohols 5b,d were synthesized accordꢀ
ing to known procedures.17,25 Nitrates of amino alcohols 1g—l
were prepared according to procedures described earlier.1,18,19
Nitration of amino alcohols was carried out with the use of
freshly distilled HNO3 (d = 1.51).
Synthesis of nitrates of amino alcohols 1a,b,e,f,i (general
procedure). Amino alcohol (10 mmol) was added portionwise to
HNO3 (0.12—0.2 mol) with stirring and cooling to 0—4 °C. The
reaction mixture was kept at 0—2 °C for 30—90 min and then
poured onto ice (5 g per milliliter of the starting HNO3). The
precipitate that formed was filtered off, washed with ice water,
dried, and recrystallized.
Nꢀ(5ꢀNitroxyꢀ3ꢀazoniapentyl)ꢀ4ꢀnitrobenzamide nitrate (1a).
Reagents and conditions: HNO3 (0.15 mol), 45 min. The yield
was 94%, m.p. 143—145 °C (with decomp.). After recrystallizaꢀ
tion from H2O, m.p. 148—150 °C (with decomp.).
Nꢀ(6ꢀNitroxyꢀ3ꢀazoniahexyl)ꢀ4ꢀnitrobenzamide nitrate (1b).
Reagents and conditions: HNO3 (0.12 mol), 1 h. The yield was
85%, m.p. 138—140 °C (with decomp.). After recrystallization
from a 1 : 1.3 H2O—PriOH mixture, m.p. 139—140 °C (with
decomp.).
N,N´ꢀBis(5ꢀnitroxyꢀ3ꢀazoniapentyl)oxamide dinitrate (1e).
Reagents and conditions: HNO3 (0.20 mol), 1 h. The yield was
82%, m.p. 144—146 °C (with decomp.). After recrystallization
from a 1% HNO3 aqueous solution, m.p. 152—153 °C (with
decomp.).
N,N´ꢀBis(6ꢀnitroxyꢀ3ꢀazoniahexyl)oxamide dinitrate (1f).
Reagents and conditions: HNO3 (0.20 mol), 1.5 h. The yield
was 86%, m.p. 156—157 °C (with decomp.). After recrystallizaꢀ
tion from a 1% aqueous HNO3 solution, m.p. 157—158 °C (with
decomp.).
Nꢀ(2ꢀNitroxyethyl)ethylenediammonium dinitrate (1g) was
prepared according to a procedure described earlier.19 Reagents
and conditions: 5a (20 mmol), HNO3 (80 mmol), CH2Cl2
(35 mL), Ac2O (32 mmol). The yield was 58%, m.p. 116—120 °C
(with decomp.). After recrystallization from MeOH, m.p.
125—127 °C (with decomp.).
Nꢀ(6ꢀHydroxyꢀ3ꢀazoniahexyl)ꢀ4ꢀnitrobenzamide
(7b).
Reagents and conditions: 5b (0.12 mol), 6a (0.10 mol),
PriOH (20 mL), 80—85 °C, 7 h. The yield was 80%, m.p.
129—132 °C. After recrystallization from a CH2Cl—CH2Cl, m.p.
134—136 °C.
4ꢀAcetamidoꢀNꢀ(5ꢀhydroxyꢀ3ꢀazoniapentyl)benzamide (7c).
Reagents and conditions: 5a (0.15 mol), 6b (0.10 mol),
BusOH (20 mL), 100—105 °C, 10 h; MeCN (100 mL) after
cooling to –10 °C. The yield was 58%, m.p. 151—154 °C. After
recrystallization from a 1 : 1.5 BusOH—MeCN mixture, m.p.
160—162 °C.
Nꢀ(5ꢀHydroxyꢀ3ꢀazoniapentyl)nicotinamide (7d). Reagents
and conditions: 5a (0.10 mol), 6c (0.10 mol), without a solvent,
80—85 °C, 6.5 h. Volatile products were removed at 130—140 °C
(1 Torr). The yield was 99.5%, m.p. 71—74 °C. After recrystalliꢀ
zation from a 1 : 44 : 71 PriOH—CHCl3—CCl4 mixture, m.p.
76—77 °C.
N,N´ꢀBis(5ꢀhydroxyꢀ3ꢀazoniapentyl)oxamide (7e). Reagents
and conditions: 5a (0.20 mol), 6d (0.10 mol), MeOH (80 mL),
60 °C, 0.5 h (in the course of stirring of the components, the
reaction mixture spontaneously warmed up to 40—50 °C). The
yield was 80%, m.p. 127—129 °C. After recrystallization from a
1 : 4.4 MeOH—MeCN mixture, m.p. 133—134 °C.
N,N´ꢀBis(6ꢀhydroxyꢀ3ꢀazoniahexyl)oxamide (7f). Reagents
and conditions: 5b (0.20 mol), 6d (0.10 mol), PriOH
(100 mL), 60 °C, 0.5 h (the reaction mixture spontaneously
warmed up). The yield was 92%, m.p. 164—167 °C. After reꢀ
crystallization from a 1 : 20 PriOH—MeOH mixture, m.p.
169—171 °C.
N,N´ꢀBis(5ꢀhydroxyꢀ3ꢀazoniapentyl)succinodiamide (7g).
Reagents and conditions: 5a (0.25 mol), 6e (0.10 mol), BusOH
(50 mL), 90—95 °C, 25 h, cooling to 0 °C. The yield was
54%, m.p. 112—114 °C. After recrystallization from a 1 : 4
MeOH—MeCN mixture, m.p. 115—116 °C.
Synthesis of oxazolidinꢀ2ꢀones and tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀ
ones 8a,b,e,f—l (general procedure). Potassium hydrogen carꢀ
bonate (or NaHCO3) was added portionwise with stirring
and heating to a solution of nitrate of amino alcohol (10 mmol).
The reaction mixture was kept at 20—60 min and then cooled
to 20 °C. Compounds 8a,b,e, which precipitated upon coolꢀ
ing, were filtered off, washed with ice water, dried, and reꢀ
crystallized. Compounds 8f—l, which are readily soluble in waꢀ
ter, were isolated as follows: the reaction solution was concenꢀ
trated to dryness (rotary evaporator, 10 Torr, 25 °C), the prodꢀ
uct was extracted from the residue with an organic solvent,
the solvent was removed in vacuo, and the residue was recrysꢀ
tallized.
N,N´ꢀBis(3ꢀnitroxypropyl)ethylenediammonium dinitrate (1i).
Reagents and conditions: HNO3 (0.20 mol), 30 min. The yield
was 91%, m.p. 139—141 °C (with decomp.). After recrystallizaꢀ
tion from a 5% aqueous HNO3 solution, m.p. 148—149 °C (with
decomp.).
4ꢀNitroꢀNꢀ[2ꢀ(2ꢀoxooxazolidinꢀ3ꢀyl)ethyl]benzamide (8a).
Reagents and conditions: H2O (115 mL), 65—70 °C, KHCO3
(25 mmol), 20 min. The yield was 89%, m.p. 182—184 °C. After
recrystallization from a 1 : 5 CCl4—MeCN mixture, m.p.
183—184 °C.
Synthesis of amido amino alcohols 7a—g (general procedure).
A mixture of diamino alcohol, ester, and a solvent was refluxed
4ꢀNitroꢀNꢀ[2ꢀ(2ꢀoxotetrahydroꢀ1,3ꢀoxazinꢀ3ꢀyl)ethyl]benzꢀ
amide (8b). Reagents and conditions: H2O (75 mL), 50—60 °C,

Transformations of nitro esters of amino alcohols
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
2229
KHCO3 (30 mmol), 30 min. The yield was 90%, m.p.
205—207 °C. After recrystallization from MeCN, m.p.
207—209 °C.
N,N´ꢀBis[2ꢀ(2ꢀoxooxazolidinꢀ3ꢀyl)ethyl]oxamide (8e). Reꢀ
agents and conditions: H2O (120 mL), 50—55 °C, KHCO3
(50 mmol), 30 min. The yield was 85%, m.p. 207—208 °C. After
recrystallization from a 1 : 1 MeOH—H2O mixture, m.p.
211—213 °C.
N,N´ꢀBis[2ꢀ(2ꢀoxotetrahydroꢀ1,3ꢀoxazinꢀ3ꢀyl)ꢀ
ethyl]oxamide (8f). Reagents and conditions: H2O (40 mL),
55—60 °C, KHCO3 (50 mmol), 60 min, extraction with hot
MeCN. The yield was 70%, m.p. 192—195 °C. After recrystalliꢀ
zation from MeCN, m.p. 199—201 °C.
Nꢀ(2ꢀAmmonioethyl)oxazolidinꢀ2ꢀone nitrate monohydrate
(8g). Reagents and conditions: H2O (10 mL), 20 °C, KHCO3
(20 mmol), 4 h. The reaction solution was concentrated and the
residue was recrystallized from a 1 : 2 MeOH—CHCl3 mixture.
The yield was 55%, m.p. 97—99 °C.
1,2ꢀBis(2ꢀoxooxazolidinꢀ3ꢀyl)ethane (8h). Reagents and conꢀ
ditions: H2O (37 mL), 50—55 °C, KHCO3 (50 mmol), 60 min,
extraction with a 1 : 2 MeOH—CH2Cl2 mixture. The yield was
86%, m.p. 102—105 °C. After recrystallization from PriOH,
m.p. 107—108 °C (cf. lit. data20: m.p. 107 °C).
1,2ꢀBis(2ꢀoxotetrahydroꢀ1,3ꢀoxazinꢀ3ꢀyl)ethane (8i). Reꢀ
agents and conditions: H2O (30 mL), 55—60 °C, KHCO3
(50 mmol), 30 min, extraction with CH2Cl2. The yield was
79%, m.p. 129—131 °C. After recrystallization from a 1 : 3
CHCl3—nꢀheptane mixture, m.p. 134—135 °C.
J ≅ 8.5 Hz); 8.31 (d, 2 H, CHCNO2, J ≅ 8.5 Hz); 8.95 (br.t, 1 H,
CONH, J ≅ 5.6 Hz).
Polymerization of 1a. A solution of 85% KOH (0.2 g, 3 mmol)
in MeOH (5 mL) was added dropwise with stirring and cooling
to 15 °C to a mixture of compound 1a (1.08 g, 3 mmol) and
MeOH (10 mL). The reaction mixture was kept at 20 °C for 1 h.
The inorganic precipitate that formed was filtered off and washed
with MeOH. Dichloromethane (20 mL) was added to the filꢀ
trate and the inorganic precipitate that formed was filtered off.
The filtrate was concentrated in vacuo to obtain a resinous yelꢀ
low compound in a yield of 0.88 g. The compound solidified
upon heating to 50 °C for 0.5 h. Then MeCN (25 mL) was added
to the compound and the reaction mixture was refluxed. The
resulting solution was filtered and the filtrate was cooled. The
precipitate that formed was filtered off, washed with MeCN,
and dried to obtain compound 4 in a yield of 0.64 g (72%).
Found (%): C, 43.85; H, 4.85; N, 18.50. (C11H14N4O6)n. Calꢀ
culated (%): C, 44.30; H, 4.73; N, 18.78. For compound 4, the
"averaged" formula of the macromolecule is given; n was calcuꢀ
lated based on the 1H NMR spectroscopic data (DMSOꢀd6),
δ: 2.60—4.40 (br.m, 79 H, CH2N, NH); 4.80 (br.t, 2 H,
CH2ONO2, J ≅ 4.5 Hz); 8.22 (m, 36 H, CH, AB system, ∆ν
≅
≅
AB
50.0 Hz, JAB ≅ 9.0 Hz); 9.02 (br.t, 9 H, CONH, JNH—CH
5.0 Hz). IR (KBr pellets), ν/cm–1: 3336, 1662, 1539 (NHCO);
3107, 3073, 1598, 836 (Ar); 2699, 2427 (NH2+); 2928, 2852,
1477, 1431 (CH2); 1644 sh, 1294 (ONO2); 1518, 1346 (NO2);
1383 (NO3–).
This study was financially supported by the Interꢀ
national Science and Technology Center (ISTC,
Grant 1550).
Oxazolidinꢀ2ꢀone (8j). Reagents and conditions: H2O
(8.5 mL), 50—55 °C, KHCO3 (30 mmol), 20 min, extraction
with CH2Cl2. The yield was 91%, m.p. 83—87 °C. After recrysꢀ
tallization from a 1 : 1 CHCl3—CCl4 mixture, m.p. 89—90 °C
(cf. lit. data12: m.p. 90—91 °C).
Tetrahydroꢀ1,3ꢀoxazinꢀ2ꢀone (8k) was prepared analogously
to compound 8j. The yield was 87%, m.p. 79—81 °C. After
recrystallization from a 1 : 5 CHCl3—CCl4 mixture, m.p.
82—84 °C (cf. lit. data21: m.p. 80 °C).
References
1. P. Naoum and H. Ulrich, Germ. Pat. 500407, 1929, 1930;
C. 1930 II 1937.
3ꢀ(2ꢀNitroxyethyl)oxazolidinꢀ2ꢀone (8l). Reagents and conꢀ
ditions: H2O (14 mL), 40—45 °C, KHCO3 (20 mmol), 60 min,
extraction with CH2Cl2. The yield was 86%, m.p. 24—28 °C.
After recrystallization from a 1 : 2 CHCl3—CCl4 mixture, m.p.
30—32 °C.
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3ꢀnitroꢀ3ꢀazoniapentyl)ꢀ4ꢀnitrobenzamide (3). A solution of 85%
KOH (0.66 g, 10 mmol) in MeOH (7 mL) was added dropwise
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1511, 1345 (NO2); 3413, 1076 (OH); 3357, 1537 sh, 1632
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1
(CONH); 1595, 1495, 720 (Ar). H NMR (DMSOꢀd6), δ: 3.40
(t, 2 H, CH2N(NO2), J ≅ 5.6 Hz); 3.45—3.56 (dt, NHCH2,
JCH,CH ≅ JCH,NH ≅ 5.6 Hz); 3.65 (t, 2 H, CH2CH2OH, J ≅
7.6 Hz); 4.28 (t, 2 H, CH2OH, J ≅ 7.6 Hz); 8.04 (d, 2 H, CHC,

2230
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Received February 5, 2003;
in revised form June 17, 2003