The first synthesis of nitro-substituted cyclopropanes and spiropentanes via oxidation of the corresponding amino derivatives

Article abstract of DOI:10.1016/j.tetlet.2009.03.165

A novel approach to nitro-substituted cyclopropanes and spiropentanes via oxidation of the corresponding amines with dimethyldioxirane is reported. The method is used successfully for the preparation of a series of nitrocyclopropanes as well as for the first synthesis of 1,4-dinitrospiro[2.2]pentane.

Full text of DOI:10.1016/j.tetlet.2009.03.165

Tetrahedron Letters 50 (2009) 2793–2796
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Tetrahedron Letters
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The first synthesis of nitro-substituted cyclopropanes and spiropentanes
via oxidation of the corresponding amino derivatives
*
Yuliya A. Volkova, Olga A. Ivanova , Ekaterina M. Budynina, Eugene V. Revunov, Elena B. Averina
Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119992, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel approach to nitro-substituted cyclopropanes and spiropentanes via oxidation of the correspond-
ing amines with dimethyldioxirane is reported. The method is used successfully for the preparation of a
series of nitrocyclopropanes as well as for the first synthesis of 1,4-dinitrospiro[2.2]pentane.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 17 February 2009
Revised 14 March 2009
Accepted 24 March 2009
Available online 28 March 2009
Keywords:
Cyclopropanes
Oxidation
Nitro-compounds
Dimethyldioxirane
Taking aniline production as an example, the general logic of or-
ganic synthesis is to consider nitro-compounds as precursors of
amino derivatives. However, in some particular cases, it is neces-
sary to use the reverse process for the synthesis of, for example,
nitrocyclopropanes. Nitro- and polynitro-cyclopropanes are of con-
siderable interest as potential high energy materials where the
strained cyclopropane-containing skeleton is in favorable conjunc-
tion with explosophore nitro functionalities.1 The synthesis of ni-
oxidation of the amino group, seems to be an improved alternative
to the methods proposed earlier. Herein, we report a novel syn-
thetic approach to nitro-substituted cyclopropanes and spiropen-
tanes via oxidation of aminocyclopropane derivatives.
It is well known that the oxidation of substituted aminocyclopro-
panes under different oxidation conditions leads to ring-opened
products.11 In this connection, the main goal of our investigation in-
volved the search for appropriate conditions for the chemoselective
oxidation of an amino group wherein a cyclopropane or spirocyclic
system would be not affected.
For our investigation we used commercially available aminocy-
clopropane 1a and various other aminocyclopropanes and spir-
opentanes 1b–g which were prepared via a known and efficient
synthetic sequence12 as shown in Scheme 1.13 The transformations
of 3b–g into 6b–g were carried out without isolation of the inter-
mediate azides 4b–g and the products of Curtius rearrangement
5b–g. The hydrochlorides 6b–g were purified by recrystallization
before conversion into the corresponding amines 1b–g.
tro-substituted cyclopropanes is
a complicated procedure in
comparison with the preparation of their open-chain analogs.1,2
Methods for the direct introduction of nitro group(s) into three-
membered rings are impractical due to considerable decomposi-
tion and poor yields of the desired products.3 A few approaches
to nitrocyclopropanes consist of the formation of a small ring from
precursors that already contain nitro groups. Among these meth-
ods are the 1,3-elimination of
zotization of nitropyrazolines,5 [1+2] cycloaddition of
nitrocarbenes to alkenes,6 reaction of
,b-unsaturated nitro-com-
c
-X-substituted nitropropanes,4 dea-
a
pounds with sulfur ylides and related processes,7 etc. Recently,
we proposed novel approaches to nitro derivatives of triangulanes8
via [1+2] cycloaddition of ethyl nitrodiazoacetate to methylenecy-
clopropanes9 and to 1,1-dinitrocyclopropanes through [3+2] cyclo-
addition of diazo-compounds to dinitroethenes.10 However, all
these methods have disadvantages such as the formation of com-
plex mixtures of products, low yields and difficult to access start-
ing materials. Therefore, the transformation of an N-containing
functional group(s) in a small ring into a nitro group, for example,
According to the literature, the most efficient oxidants for the
transformation of primary amino groups at secondary alkyl carbons
into a nitro functionality are m-chloroperbenzoic acid (MCPBA),14
ozone,15 and dimethyldioxirane (DMDO).16 We carried out a brief
survey of these oxidizing agents employing aminocyclopropanes
1b,e as model substrates for optimization of the oxidation condi-
tions (Table 1). Unfortunately, the simplest aminocyclopropane 1a
was found to be an unsuitable model due to its high volatility.
We found that the oxidation of amines 1b,e with MCPBA affor-
ded 4,5-dihydroisoxazoles 7b,e as the only products (Table 1,
entries 1 and 2). The formation of 7b,e proceeded presumably via
oxidation of 1b,e into unstable nitrosocyclopropanes A followed
* Corresponding author. Tel.: +7 915 4044176.
E-mail address: iv@org.chem.msu.ru (O.A. Ivanova).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.165

2794
Y. A. Volkova et al. / Tetrahedron Letters 50 (2009) 2793–2796
R3
R3
R3
R1
R2
R1
R2
R1
R2
R1
R2
R3
t-BuOH
N2CHCO2Et
Rh2(OAc)4
1) N2H4·H2O
2) HCl
3) NaNO2
Δ
CO2Et
3b-g
CON3
4b-g
NHCO2But
5b-g
2b-g
HCl
: R1 = Ph, R2, R3 = H
1-6, b
1
2
: R = C4H9, R , R3 = H
c
R3
R3
R1
R2
R1
R2
d: R1, R3 = -(CH2)4-, R2 = H
NaOH
e: R1, R2 = -(CH2)3-, R3 = H
1
2
: R , R = -(CH2)2-, R3 = H
f
g
NH3Cl
NH2
1b-g
1
2
: R , R = -CH2-CH(NH2)-, R3 = H
6b-g
Scheme 1. Synthesis of starting aminocyclopropanes 1b–g.
Table 1
not been reported previously. At the same time, it seems to be
analogous to the well-known 1,3-sigmatropic vinylcyclopropane–
cyclopentene rearrangement and related processes.17
Screening of oxidants with aminocyclopropanes 1b,e
Entry
1
Amine
[O]
Product
Unfortunately, ozone was also found to be unsuitable as an oxi-
dant for aminocyclopropanes 1b,e affording the desired nitrocyclo-
propanes 8b,e in very poor yields (Table 1, entries 3 and 4).
However, DMDO proved to be a suitable oxidizing agent. In spite
of the low conversion of 1b into target nitrocyclopropane 8b (Table
1, entry 5), DMDO was efficient for the oxidation of 1e into the cor-
responding nitrocyclopropane 8e in a good yield (Table 1, entry 6).
We therefore utilized a 0.08 M solution of DMDO18 in acetone as
the oxidant for the conversion of a series of aminocyclopropanes
1a,c,d,f and hydrochloride 6g into the corresponding nitrocyclo-
propanes 8a,c,d,f,g (Table 2).
Ph
N
O
7b, 24%
MCPBAa
Ph
1b
NH2
N
2
3
MCPBAa
O
NH2
1e
7e, 54%
O
Ph
Ph
Ph
+
b
O3
OH
NH2
NO2
1b
8b, 2%
27%
Table 2
b
Oxidation of amines 1a,c,d,f and hydrochloride 6g with DMDO
4
5
O3
NO2
8e, 3%
NH2
NH2
NH2
1e
DMDO
NH2
R
R
NO2
acetone
Ph
+
N
Ph
Ph
7b, 42%
DMDOc
DMDOc
O
Entry
1
Amine
Product
Yield (%)
40a
NO2
1b
8b, 7%
NH2
NO2
8a
1a
6
NO2
8e, 60%
1e
Bu
Bu
2
3
61a
76a
NH2
NO2
1c
8c
a
Reaction conditions: tenfold molar excess of MCPBA, 1,2-dichloroethane, reflux,
4 h.
b
Reaction conditions: 6 wt % O3/O2–SiO2, 1.8 mL/s, À78 °C, 50 min.
c
Reaction conditions: 0.08 M DMDO in acetone, sevenfold molar excess of
DMDO, rt, 1 h, dark.
NH2
NO2
1d
8d
8f
by ring cleavage and subsequent formation of the five-membered
heterocycle 7 (Scheme 2). Circumstantial evidence for intermedi-
ate A was obtained by the immediate appearance of a blue color
when 1b,e were treated with MCPBA. To the best of our knowledge,
such rearrangement of nitrosocyclopropanes into isoxazolines has
4
56a
NO2
NH2
H2N
1f
HCl
O2N
m-CPBA
R1
R1
R2
R1
R2
N
5
56b
R2
NH2
N
O
O
HCl
NH2
NO2
8g
1b,e
A
7b,e
6g
7b: R1 = H, R2 = Ph, 24%
a
Reaction conditions: 0.08 M DMDO in acetone, sevenfold molar excess of
DMDO, rt, 1 h, dark.
7e: R1, R2 = -(CH2)3-, 54%
b
Reaction conditions: 0.08 M DMDO in acetone–water (9:1), tenfold molar
excess of DMDO per amino group, rt, 24 h, dark.
Scheme 2. Oxidation of aminocyclopropanes 1b,e into isoxazolines 7b,e.

Y. A. Volkova et al. / Tetrahedron Letters 50 (2009) 2793–2796
2795
12. (a) Tomilov, Yu. V.; Klimenko, I. P.; Shulishov, E. V.; Nefedov, O. M. Izv. RAN. Ser.
Khim. 2000, 49, 1210. Russ. Chem. Bull. 2000, 49, 1207; Chem. Abstr. 2001, 134,
42091; (b) Hoffman, H. A.; Burger, A. J. Am. Chem. Soc. 1952, 74, 5485; (c) Feng,
G.; Wang, D.; Zheng, Q.; Wang, M. Tetrahedron: Asymmetry 2006, 17, 2775; (d)
Eaton, P. E.; Ravi Shankar, B. K.; Price, G. D.; Pluth, J. J.; Gilbert, E. E.; Alster, J. J.
Org. Chem. 1984, 49, 185; (e) Mangelinckx, S.; De Kimpe, N. Tetrahedron Lett.
2003, 44, 1771; (f) Salgado, A.; Huybrechts, T.; Eeckhaut, A.; Van der Eycken, J.;
Szakonyi, Z.; Fülöp, F.; Tkachev, A.; De Kimpe, N. Tetrahedron 2001, 57, 2781;
Thus, we found that the oxidation of monoamines 1a,c,d,f with
DMDO proceeded chemoselectively resulting in the corresponding
nitrocyclopropanes 8a,c,d,f in good yields (Table 2, entries 1–4).19
It should be noted that the use of MCPBA in the case of amines 1c,d
was also successful and led to the corresponding nitrocyclopro-
panes 8c,d as single products in 50% and 54% yields, respectively.
Finally, an important application of the reported oxidation pro-
cedure was the successful synthesis of 1,4-dinitrospiro[2.2]pen-
tane (8g) (Table 2, entry 5).20 Dinitrospiropentane 8g is a novel
representative of polynitrotriangulanes in which each ring is
substituted with a nitro group. Earlier, a 1,2-dinitrospiro[2.2]pen-
tane bearing both nitro functionalities on the same cyclopropane
ring was synthesized via oxidative cyclization in moderate yield.4g
For the synthesis of dinitrospiropentane 8g we simplified the oxi-
dation procedure by utilization of the double hydrochloride salt 6g
instead of the free diamine 1g which was less stable and less con-
venient to work with. The oxidation of 6g into the corresponding
dinitrospiropentane 8g was realized under the standard conditions
using a tenfold molar excess of DMDO per amino group.
In conclusion, DMDO was found to be an efficient oxidizing
agent for the conversion of amino-substituted cyclopropanes and
spiropentanes into the corresponding nitrocyclopropane deriva-
tives. The reported method is chemoselective and proceeds under
mild conditions and in moderate to good yields to afford a variety
of strained nitro-substituted compounds bearing a cyclopropane
ring and spiroannulated moieties which are difficult to access via
other synthetic approaches.
(g) De Kimpe, N.; Boeykens, M.; Tehrani, K. A. J. Org. Chem. 1994, 59,
8215.
13. General procedure for the synthesis of azides 4b–g: hydrazine hydrate (4 mL)
was added to a solution of ethyl carboxylate 3 (0.01 mol) in CH3OH (30 mL)
and the resulting mixture was maintained at room temperature for 3 d. The
solvent was evaporated and the resulting white crystalline residue was
dissolved in water (15 mL) and concentrated HCl (3.0 mL) was added
dropwise with stirring over 30 min under cooling with an ice-salt-bath. The
mixture was diluted with Et2O (15 mL) and a solution of NaNO2 (1.4 g) in water
(5 mL) was added dropwise over 30 min at 5 °C. The organic layer was
separated and the aqueous phase was extracted with Et2O (2 Â 10 mL). The
combined organic layer was washed with saturated aqueous NaHCO3 solution
(3 Â 5 mL), water (5 mL), and dried over MgSO4. The solvent was removed
under reduced pressure and the crude product was used without purification.
1,4-Diazidospiro[2.2]pentane
(4g):
mixture
of
four
isomers
A:B:C:D = 50:20:20:10; Rf 0.49 (CHCl3); 1H NMR (400 MHz, CDCl3) of the
mixture of four isomers: d 1.50–1.69 (m, 12H, CH2), 1.71–1.76 (m, 2H, CH2, B),
1.85–1.91 (m, 2H, CH2, A), 2.05–2.15 (m, 4H, CH, C+D), 2.17–2.20 (m, 2H, CH,
B), 2.23–2.29 (m, 2H, CH, A); 13C NMR (100 MHz, CDCl3): isomer A: d 10.5
(2CH2), 18.3 (2CH), 26.5 (C), 176.6 (2C); isomer B: d 13.1 (2CH2), 19.6 (2CH),
26.2 (C), 176.4 (2C); isomer C: d 13.4 (2CH2), 19.7 (2CH), 26.6 (C), 176.6 (2C);
isomer D: d 13.9 (2CH2), 20.9 (2CH), 26.6 (C), 176.6 (2C).
General procedure for the synthesis of amine hydrochlorides 6b–g:
Method A. A solution of azide 4b,e–g (10 mmol) in tert-butanol (40 mL) was
refluxed until completion of nitrogen evolution (about 12 h). The solvent was
evaporated and the residue was treated with a saturated 1,4-dioxane solution
of HCl (20 mL). The resulting mixture was stirred for 2 h at room temperature
and the solvent was removed under reduced pressure. The crude product was
purified by recrystallization from chloroform or methanol.
Method B. A solution of azide 4c,d (10 mmol) in toluene (12 mL) was refluxed
until completion of nitrogen evolution (about 6 h). The reaction mixture was
allowed to cool to room temperature and then treated dropwise with
concentrated HCl (20 mL). The resulting mixture was refluxed for 2 h and
concentrated under reduced pressure. The crude product was purified by
recrystallization from chloroform or methanol.
Caution: Although we have not met any problems in handling
these compounds, full safety precautions should be taken due to
their potentially explosive nature.
Acknowledgments
Spiro[2.2]pentane-1,4-diamine dihydrochloride (6g): mixture of four isomers
A:B:C:D = 35:30:25:10; 1H NMR (400 MHz, D2O) of the mixture of four
isomers: d 1.36–1.47 (m, 10H, CH2), 1.54–1.61 (m, 6H, CH2), 3.11 (dd, 3J = 3.8,
7.0 Hz, 2H, CH, D), 3.16 (dd, 3J = 3.9, 7.0 Hz, 2H, CH, B), 3.22 (dd, 3J = 3.9, 7.5 Hz,
2H, CH, C), 3.30 (dd, 3J = 5.3, 6.5 Hz, 2H, CH, A); 13C NMR (100 MHz, CDCl3):
isomer A: d 10.7 (1J = 169 Hz, 2CH2), 15.5 (C), 28.8 (1J = 190 Hz, 2CH); isomer B:
d 8.72 (1J = 167 Hz, 2CH2), 15.8 (C), 27.9 (1J = 190 Hz, 2CH); isomer C: d 9.0
We thank the Division of Chemistry and Materials Science RAS
(Program N 1.5) and the Russian Foundation for Basic Research
(Projects 07-03-00685-a, 09-03-00244-a) for financial support of
this work.
(1J = 168 Hz, 2CH2), 16.1 (C), 26.9 (1J = 188 Hz, 2CH), isomer D:
d 11.0
(1J = 167 Hz, 2CH2), 16.1 (C), 28.5 (1J = 190 Hz, 2CH).
References and notes
General procedure for the isolation of free amines 1b–f. Hydrochloride 6 (1 mmol)
was treated with a 25 M aqueous solution of NaOH (0.05 mL). The resulting
solution was extracted with CH2Cl2 (3 Â 5 mL). The combined organic layer
was dried over 4 Å molecular sieves and the solvent was removed under
reduced pressure. The crude amine was employed immediately in the
oxidation reaction.
1. (a) Agrawal, J. P.; Hodgson, R. D. Organic Chemistry of Explosives; Wiley-VCH:
Chichester, 2007; (b) Ballini, R.; Palmieri, A.; Fiorini, D. ARKIVOC 2007, vii, 172.
2. (a) Ono, N. In The Nitro Group in Organic Synthesis; Feuer, H., Ed.; Wiley-VCH:
New York, 2001; pp 3–29; (b) Feuer, H. The Chemistry of Nitro and Nitroso
Groups; Part I. NY, 1981.
14. (a) Gilbert, K. E.; Borden, W. T. J. Org. Chem. 1979, 44, 659; (b) Emmons, W. D. J.
Am. Chem. Soc. 1957, 79, 5528.
3. (a) Hass, H. B.; Shechter, H. J. Am. Chem. Soc. 1953, 75, 1382; (b) Haner, R.;
Maetzke, Th.; Seebach, D. Helv. Chim. Acta 1986, 69, 1655.
15. (a) Keinan, E.; Mazur, Y. J. Org. Chem. 1977, 42, 844; (b) Bailey, P. S.; Keller, J. E. J.
Org. Chem. 1968, 33, 2680; (c) Zajac, W. W.; Walters, T. R.; Woods, J. M. J. Org.
Chem. 1989, 54, 2468; (d) Bailey, P. S.; Carter, T. P.; Southwick, L. M. J. Org.
Chem. 1972, 37, 2997; (e) Bailey, P. S.; Keller, J. E.; Carter, T. P. J. Org. Chem.
1970, 35, 2777.
16. (a) Murray, R. W.; Rajadhyaksha, S. N.; Mohan, L. J. Org. Chem. 1989, 54, 5783;
(b) Murray, R. W.; Jeyaraman, R.; Mohan, L. Tetrahedron Lett. 1986, 21, 2335.
17. (a) Hudlicky, T.; Becker, D. A.; Fan, R. L.; Kozhushkov, S. I. In Houben-Weyl; de
Meijere, A., Ed.; Formation of Five-membered Rings; Thieme: Stuttgart, 1997;
Vol. E 17c, pp 2538–2565; (b) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.;
Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165.
4. (a) Russell, G. A.; Makosza, M.; Hershberger, J. J. Org. Chem. 1979, 44, 1195; (b)
Kai, Y.; Knochel, P.; Kwiatkowski, S.; Dunitz, J. D.; Oth, J. F. M.; Seebach, D.;
Kalinowski, H.-O. Helv. Chim. Acta 1982, 65, 137; (c) Kuwajuma, I.; Ando, R.;
Sugawara, T. Tetrahedron Lett. 1983, 24, 4429; (d) Zindel, J.; de Meijere, A. J. Org.
Chem. 1995, 60, 2968; (e) Zindel, J.; Zeeck, A.; Konig, W. A.; de Meijere, A.
Tetrahedron Lett. 1993, 34, 1917; (f) Yu, J.; Falck, J. R.; Moiskowski, Ch. J. Org.
Chem. 1992, 57, 3757; (g) Wade, P. A.; Kondracki, P. A.; Carroll, P. J. J. Am. Chem.
Soc. 1991, 113, 8807.
5. (a) Parham, W. E.; Serres, C.; O’Connor, P. R. J. Am. Chem. Soc. 1958, 80, 588; (b)
Mustafa, A.; Harhash, A. H. E. J. Am. Chem. Soc. 1954, 76, 1383; (c) Parham, W. E.;
Braxton, H. G., Jr.; Serres, C. J. Org. Chem. 1961, 26, 1831.
18. For the preparation of DMDO solution, see: Crandall, J. K.; Batal, D. J.; Sebesta,
D. P.; Lin, F. J. Org. Chem. 1991, 56, 1153.
6. O’Bannon, P. E.; Dailey, W. P. Tetrahedron 1990, 46, 7341.
7. (a) Asunskis, J.; Shechter, H. J. Org. Chem. 1968, 33, 1164; (b) Sakakibara, T.;
Sudoh, R. J. Chem. Soc., Chem. Commun. 1977, 7; (c) Perekalin, V. V.; Lipina, E. S.;
Berestovitskaya, V. M.; Efremov, D. A. Nitroalkenes. Conjugated Nitro
Compounds; Wiley: New York, 1994. pp 1–256.
8. Zefirov, N. S.; Kozhushkov, S. I.; Kuznetsova, T. S.; Kokoreva, O. V.; Lukin, K. A.;
Ugrak, B. I.; Trach, S. S. J. Am. Chem. Soc. 1990, 112, 7702.
9. Ivanova, O. A.; Yashin, N. V.; Averina, E. B.; Grishin, Yu. K.; Kuznetsova, T. S.;
Zefirov, N. S. Izv. RAN. Ser. Khim. 2001, 50, 2008; . Russ. Chem. Bull. 2001, 50,
21011; . Chem. Abstr. 2002, 137, 247443.
19. General procedure for the oxidation of amines 1b–f with DMDO. Free amine 1
(0.5 mmol) in acetone (1 mL) was added to a 0.08 M solution of DMDO in
acetone (45 mL). The resulting mixture was maintained at room temperature
for 1 h in the dark. The solvent was removed on a rotary evaporator under
normal pressure. The crude product was purified by column chromatography
(eluent: chloroform). The resulting nitrocyclopropanes 8a,c,d,f are stable on
storage at 5 °C over a long time.
20. Oxidation of amine hydrochloride 6g with DMDO.
A solution of amine
hydrochloride 6g (0.5 mmol) in distilled water (3 mL) was added to a 0.08 M
solution of DMDO in acetone (125 mL). The resulting mixture was maintained
at room temperature for 1 h in the dark. Acetone was removed on a rotary
evaporator under normal pressure. The resulting aqueous solution was
extracted with chloroform (3 Â 5 mL). The combined organic layer was dried
over 4 Å molecular sieves and the solvent was removed under reduced
10. (a) Budynina, E. M.; Averina, E. B.; Ivanova, O. A.; Yashin, N. V.; Kuznetsova, T.
S.; Zefirov, N. S. Synthesis 2004, 16, 2609; (b) Ivanova, O. A.; Budynina, E. M.;
Averina, E. B.; Kuznetsova, T. S.; Grishin, Yu. K.; Zefirov, N. S. Synthesis 2007, 13,
2009.
11. Ryu, I.; Murai, S. In Houben-Weyl; de Meijere, A., Ed.; Aminocyclopropanes;
Thieme: Stuttgart, 1997; Vol. E 17c, pp 2034–2040.

2796
Y. A. Volkova et al. / Tetrahedron Letters 50 (2009) 2793–2796
pressure. The crude product was purified by column chromatography (eluent:
chloroform). The resulting nitrocyclopropane 8g is stable on storage at 5 °C
over a long time.
1,4-Dinitrospiro[2.2]pentane (8g): mixture of four isomers A:B:C:D = 34:30:26:10;
Rf 0.54 (CHCl3); 1H NMR (400 MHz, CDCl3): isomer A: d 1.89 (dd, 2J = 6.5,
3J = 6.2 Hz, 2H, CH2), 2.34 (dd, 2J = 6.5, 3J = 3.4 Hz, 2H, CH2), 4.88 (dd, 3J = 3.4,
6.2 Hz, 2H, CH); isomer B: d 1.91 (dd, 2J = 6.8, 3J = 7.0 Hz, 2H, CH2), 2.52 (dd,
2J = 6.8, 3J = 3.6 Hz, 2H, CH2), 4.77 (dd, 3J = 3.6, 7.0 Hz, 2H, CH); isomer C: d 2.03
(dd, 2J = 6.8, 3J = 6.7 Hz, 2H, CH2), 2.29 (dd, 2J = 6.8, 3J = 3.7 Hz, 2H, CH2), 4.69
(dd, 3J = 3.7, 6.7 Hz, 2H, CH); isomer D: d 2.13 (dd, 2J = 6.9, 3J = 6.9 Hz, 2H, CH2),
2.36 (dd, 2J = 6.9, 3J = 3.9 Hz, 2H, CH2), 4.69 (dd, 3J = 3.9, 6.9 Hz, 2H, CH); 13C
NMR (100 MHz, CDCl3): isomer A: d 17.1 (1J = 170 Hz, 2CH2), 28.4 (C), 58.5
(1J = 192 Hz, 2CH); isomer B:
(1J = 197 Hz, 2CH); isomer C:
(1J = 195 Hz, 2CH), isomer D:
d
d
d
16.3 (1J = 173 Hz, 2CH2), 30.9 (C), 59.5
16.8 (1J = 171 Hz, 2CH2), 27.5 (C), 59.9
18.0 (1J = 171 Hz, 2CH2), 26.7 (C), 58.5
(1J = 197 Hz, 2CH). MS (EI, 70 eV) m/z: 66 ([MÀ2NO2]+, 5), 65 (18), 55 (37),
53 (20), 41 (23), 39 (100), 30 (38), 27 (32). MS (ESI) calcd for C5H6N2O4 (M+H)+:
159.12, found: 159.10.