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Synthesis and intramolecular ring transformationof N,N’-dialkylated 2,6,9-triazabicyclo[3.3.1]
Cite this: Org. Biomol. Chem., 2020,
18, 9109
nonadienes†
Yumi Nakaike, a Yusuke Yoshida,b Soichi Yokoyama,
Nagatoshi Nishiwaki *b,cReceived 23rd September 2020,
Accepted 28th October 2020
DOI: 10.1039/d0ob01950jrsc.li/obc

b,c,d

Akitaka Ito

b,c

and

The ﬁrst and facile synthesis of N,N’-dialkylated 2,6,9-triazabicyclo[3.3.1]nonadienes was achieved by the[4 + 4] self-condensation of β-formyl-β-nitroenamine in the presence of ammonium acetate. The 2,6and 2,9-dialkylated products were found to be interconvertible when dissolved in a solvent. This isomerization proceeds through intramolecular ring transformation via a common intermediate underequilibrium.

Introduction
β-Formyl-β-nitroenamine 1 possesses multiple functionalities
such as a formyl, nitro, and amino group, and a carbon–
carbon double bond with biased electron density, which bringabout diverse reactivities.1 Two electrophilic sites of 1 reactwith dinucleophiles such as hydrazines, 1,2-diamines, andketones to aﬀord nitrated pyrazoles,2 diazepines2 and phenols(Scheme 1, a),3 respectively, in which nitroenamine 1 serves as
a synthetic equivalent of nitromalonaldehyde (NMA-H). Its
sodium salt (NMA-Na) component has been used for thispurpose for a long time. However, NMA-Na should be handled
carefully because of the explosive impurity, and aqueous or
alcoholic media should be used.4 In contrast, nitroenamine 1
is safely handleable, and its high solubility in common
organic solvents allows its reaction with versatile reagents inorganic media.
The dipolar properties of nitroenamine 1 facilitate its reactions with 1,3-dicarbonyl compounds possessing both nucleophilic and electrophilic sites, and polyfunctionalized pyri-dones are synthesized through this process.5 In these reactions, a secondary amine such as piperidine is found to be asuitable base for condensation, while a tertiary amine such as
triethylamine causes no reaction, indicating that the intermediate formation of iminium species is crucial (Scheme 1, b).
Furthermore, the [4 + 2] self-condensation of 1 proceeds in thepresence of sulfonic acid to form a dinitropyridinium salt
in situ, which can be trapped by electron-rich benzenes
leading to the formation of 4-arylated 1,4-dihydropyridines(Scheme 1, c).6a

Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto University, Yoshidahonmachi, Sakyo-ku, Kyoto 606-8501, Japanb
School of Environmental Science and Engineering, Kochi University of Technology,
Tosayamada, Kami, Kochi 782-8502, Japan.
E-mail: nishiwaki.nagatoshi@kochi-tech.ac.jpcResearch Center for Molecular Design, Kochi University of Technology, Tosayamada,Kami, Kochi 782-8502, Japand
The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka,
Ibaraki, Osaka 567-0047, Japan† Electronic supplementary information (ESI) available: Spectral data and copies
of NMR spectra of compounds 2–6, crystallographic data of 2a and 3d, andtemperature-dependent NMR spectra. CCDC 2027731 and 2027735. For ESI andcrystallographic data in CIF or other electronic format see DOI: 10.1039/
d0ob01950j

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Scheme 1 Reactions using nitroenamine 1, in which the pink circles
and blue circles indicate electrophilic and nucleophilic sites,
respectively.

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Organic & Biomolecular Chemistry

These results prompted us to design a new synthetic
method for the triazabicyclic framework, including the [4 + 4]
self-condensation of nitroenamine 1. Tröger’s base7 (3,7dibenzo-2,6-diazabicyclo[3.3.1]nonane) with a V-shaped structure has attracted much attention because of its chirality,8 biological activity,9 molecular recognition ability,10 and optoelectronic properties.11 However, the bridgehead nitrogenatoms cannot be modified anymore. Hence, researchers’ attention has recently turned towards its aza-analogue, 2,6,9-triazabicyclo[3.3.1]nonane (TABN), because of the availability offurther interactions and modifiability of nitrogen atoms in the
scaﬀold.12 However, it is still diﬃcult to introduce a functionalgroup into the bicyclic framework,13 except for two examples.14,15
We focused on one of the examples, Ostercamp’s work. The
functionalized TABN derivative was first synthesized by thetreatment of NMA-Na with methylamine (Scheme 2, a).15 The
use of safely handleable nitroenamine 1 was considered to represent a general synthetic method for diverse TABNs because
the N-substituent of 1 can be easily modified. In Ostercamp’s

Scheme 2 Synthetic equivalents of NMA-H: (a) sodium salt NMA-Naand (b) 1-methyl-3,5-dinitro-2-pyridone.

Table 1

work, methylamine also serves as a nitrogen source to form anitrogen bridge, which indicates that the addition of a nitrogen source to our reaction is also necessary. In our study ofthree-component ring transformation using dinitropyridone,ammonium acetate was found to serve as an excellent nitrogensource and an activator of the substrate (Scheme 2, b),16 which
prompted us to study the synthesis of TABNs using nitroenamine 1 and ammonium acetate (Scheme 1, d).

Results and discussion
When a solution of nitroenamine 1a in ethanol was heated at
80 °C for 1 d in the presence of ammonium acetate, four kindsof TABNs 2a–5a were formed, among which 2a and 3a could
not be separated by column chromatography (Table 1, entry 1).
In the 1H NMR spectrum of one major product 2a, a singlet
signal assigned to two equivalent olefinic protons and an NH
signal showing coupling with the adjacent bridgehead protons
were observed. Hence, this isomer was determined to be a 2,6dipropyl derivative. The other major product 3a possesses anunsymmetrical structure; one of the olefinic protons wasobserved as a singlet, and the other was observed as a doublet
coupled with the adjacent NH proton, which was also supported by the 1H–1H COSY 2D NMR spectrum. The recrystallization of the 2a and 3a mixture aﬀorded a single crystal of 2a,which was subjected to X-ray crystallography to confirm thestructure (Fig. 1, left). Fortunately, a single crystal of dibenzyl
derivative 3d was obtained, and the structure was confirmed to
be a 2,9-disubstituted isomer (Fig. 1, right). The use of lower
reaction temperature increased the total yield of products 2a–5a, presumably because the competitive decomposition ofFormation of four kinds of triazabicyclic compounds 2–5

Yielda (%)
Entry

R

1
2
3
4
5
6
7b
8
9
10

Pr
Pr
Pr
Pr
Pr
i-Pr
t-Bu
–CH2Ph–CH2CHvCH2–CH2CH2OH

a

a
a
a
a
a
b
c
d
e
f

NH4OAc (equiv.)

Temp. (°C)

2

3

4

5

Total

Recovery of 1a (%)

1
1
1
2
4
1
1
1
1
1

80
50
rt
50
50
50
50
50
50
50

25
51
45
47
39
27
0
26
21
37

12
20
12
21
18
4
0
53
41
24

7
19
18
23
39
20
0
11
15
8

2
1
0
2
1
0
0
3
3
12

46
90
75
93
97
51
0
93
80
81

20
10
18
4
1
29
30
4
6
4

Determined by 1H NMR. b Non-alkylated bicyclic compound 6 was obtained in 26% yield.

9110 | Org. Biomol. Chem., 2020, 18, 9109–9116

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Organic & Biomolecular ChemistryFig. 1 ORTEP views of 2a (left, 2,6-di-Pr) and 3d (right, 2,9-di-Bn).
Thermal ellipsoids are represented at probably the 50% level. CCDC:
2027731 (2a) and 2027735 (3d).†

ammonium acetate was suppressed (entry 2). Although thisreaction proceeded even at room temperature, the total yielddecreased to an extent (entry 3). The yields of dealkylated products 4a and 5a increased when larger amounts of ammonium
acetate were used (entries 4 and 5).
The optimized conditions were applied to other nitroenamines 1b–f. Bicyclic products 2b–5b possessing bulkier isopropyl groups could be prepared by altering nitroenamine to 1b(entry 6). When tert-butyl-substituted nitroenamine 1c was
employed, the corresponding bicyclic products 2c–5c were notformed, and non-alkylated bicyclic product 6 was obtainedwith 26% yield, which was due to the easy elimination of thestable tert-butyl cation under acidic conditions (entry 7). It wasalso possible to introduce functional groups to the ring nitrogen atoms, such as benzyl, allyl, and 2-hydroxyethyl groups,
eﬃciently (entries 8–10).
All attempts to control the selectivity between 2 and 3
failed. During this study, we noticed that the 2/3 ratio changed
each time we performed 1H NMR. This observation suggeststhat there is a relationship of equilibrium between 2 and 3. To
confirm this, the single crystals of 2a and 3d used for X-ray
crystallography were dissolved in deuterated solvents, and thechange in the mole fraction ([2]/[2] + [3]) was monitored by 1H
NMR at intervals of several minutes/hours (Fig. 2). Conversion
from 2a to 3a was observed by only dissolving them in the solvents at room temperature, irrespective of the solvent, without

Paper
the formation of any detectable byproduct. A diﬀerent behavior was observed when 2a was dissolved in chloroform-d,
which might be due to a trace amount of hydrochloric acid in
the solvent. Conversely, the formation of 2d was also observed
when 3d was dissolved in deuterated solvents. The equilibrium
constants (K = [3]/[2]) were temperature-dependent, as shownin Fig. 3. The K value for 3a/2a increased upon increasing thetemperature, whereas that for 3d/2d decreased. The Gibbs
energy diﬀerences between 2 and 3 determined by the
Arrhenius-type fittings (ln K = −ΔG/RT ) reveal that 3d is morestable than 2d (ΔG < 0) in contrast to the 2a/3a system(Table 2). The diﬀerence originated from the existence of
π-stacking between the benzyl groups in 3d. In addition, the Kvalues in CD3CN were smaller than the relevant values in
CDCl3, presumably due to the polarity and/or Lewis acidity/
basicity of the solvent. These tendencies were qualitatively
reproduced by theoretical calculations. Furthermore, when amixture of 2a and 3a was heated in the presence of ammonium
acetate, nitroenamine 1a was formed in 10% yield in the reaction mixture, indicating the existence of equilibrium between
1a and TABNs 2a and 3a.
Based on these results, bicyclic products 2 and 3 are considered to be formed as shown in Scheme 3. The reaction is
initiated by the conversion of a formyl group of 1 to iminium

Fig. 3 Temperature dependences of equilibrium constants K for 3a/2a(closed squares) and 3d/2d (open squares) in CDCl3 (green) and CD3CN(red).

Table 2 Observed and calculated Gibbs energy diﬀerences in chloroform and acetonitrile

ΔG (kJ mol−1)
R

Solvent

Obsda

Calcdb

–Pr

Chloroform
Acetonitrile
Chloroform
Acetonitrile+2.40 ± 0.09
+1.58 ± 0.12
−1.36 ± 0.22
−2.38 ± 0.14

+5.22
+5.29
+1.87
+0.69

–CH2PhFig. 2 Time courses of the mole fraction of 2a (closed squares) and 3d(open squares) in C6D6 (black), CDCl3 (green) and CD3CN (red).

This journal is © The Royal Society of Chemistry 2020a

Determined using deuterated solvents. b Calculated at the B3LYP/6311+G(d,p) level.

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the conversion of nitroenamine 1 or iminium ion 7 to nitroenamine 11 (Scheme 4), which aﬀords dealkylated products 4
and 5 in a manner similar to that shown in Scheme 3.
Products 4 and 5 are also inseparable because there is arelationship between these compounds.

Conclusions

Scheme 3 A plausible mechanism for the formation of bicyclic compounds 2 and 3.

ion 7, which facilitates the attack of the less nucleophilicamino group of another molecule of 1 forming 8. After theelimination of ammonia, the formed iminium ion is attacked
by the imino group intramolecularly to form a six-memberedring. Dihydropyrimidine 10 is a common intermediate of 2
and 3. When the amino group in the side chain attacks the
4-position (Path A), 2,6-dialkyl product 2 is formed. On theother hand, 2,9-dialkyl product 3 is formed when the aminogroup attacks the 6-position of 10 (Path B). A direct rearrangement between 2 and 3 is also possible if a stable cation suchas a benzyl and allyl cation is released. However, ring transformation via intermediate 10 is considered to be more plausible based on our previous findings; 4,6-dinitro-2,8-diazabicyclo[3.3.1]nona-2-ene and 3-nitropyridine are interconvertible
under equilibrium in the presence of ammonium acetate.17
The use of larger amounts of ammonium acetate is subject to

Scheme 4 Conversion of an alkylamino group to an amino group in
the nitroenamine moiety.

9112 | Org. Biomol. Chem., 2020, 18, 9109–9116

TABN frameworks were eﬃciently constructed by the [4 + 4]
self-condensation of nitroenamine 1 in the presence ofammonium acetate. Since the N-alkyl group of 1 is easily modified, versatile TABNs were available by this protocol. The major
products, 2,6- and 2,9-dialkylated TABNs 2 and 3, were foundto be interconvertible when dissolved in a solvent and this isomerization proceeds through intramolecular ring transformation under equilibrium via the common intermediate 10.
Further studies on the physical properties of TABNs andchemical conversion using the functionalities are in progress,
and the results will be presented in due course.

Experimental section
GeneralThe melting points were determined using an SRS-Optimelt
automated melting point system. All the reagents and solventswere commercially available and used as received. The 1H
NMR spectra were measured on a Bruker Ascend-400 at
400 MHz with tetramethylsilane as an internal standard. The
13
C NMR spectra were measured on a Bruker Ascend-400 at
100 MHz, and the assignments of the 13C NMR spectra were
performed by DEPT experiments. The high-resolution mass
spectra were measured on an AB SCIEX Triple TOF 4600. The
IR spectra were recorded on a JASCO FT/IR-4200 spectrometer.
Preparation of nitroenamines 1a–f
Nitroenamines 1a–f were prepared according to our established method.18 Nitropyrimidinone was prepared in 70%
overall yield by the condensation of commercially available
1,1,3,3-tetramethoxypropane and N-methylurea in 12 M hydrochloric acid followed by nitration with nitric acid in sulfuric
acid. To a solution of pyrimidinone (310 mg, 2 mmol) in
methanol (40 mL), propylamine (410 μL, 5 mmol) was added,
and the mixture was heated under reflux for 3 h. After evaporation, the residue was extracted with hexane (3 × 30 mL), andthe removal of hexane aﬀorded NMR pure azadienamine(390 mg, 1.96 mmol, 98%) as a pale yellow oil. A solution of
azadienamine (200 mg, 1 mmol) in chloroform (5 mL) was
charged on silica gel (20 g) in a column and allowed to standat room temperature for 1 day, and then it was eluted withchloroform. The solvent was removed under reduced pressure
to give nitroenamine 1a (150 mg, 93%). Other nitroenamines
1b–f were prepared in the same way by using the corresponding amines instead of propylamine (Scheme 5).

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Organic & Biomolecular ChemistryPaper(400 MHz, CDCl3) δ 4.16 (br dd, J = 5.8, 5.8 Hz, 2H), 5.3–5.5(m, 2H), 5.8–6.0 (m, 1H, overlapped with signals of E-isomer),
7.91 (d, J = 15.2 Hz, 1H), 9.5–9.9 (br, 1H), 10.06 (s, 1H).

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4-Aza-6-hydroxy-2-nitro-2-hexenal (1f )Scheme 5

Outline of the preparative method for nitroenamines 1a–f.

4-Aza-2-nitro-2-heptenal (1a)18
Brown solid (E/Z = 76/24). (E)-Isomer; 1H NMR (400 MHz,CDCl3) δ 1.01 (t, J = 7.4 Hz, 3H), 1.74 (tq, J = 7.3, 7.4 Hz, 2H),
3.45 (dt, J = 6.8, 7.3 Hz, 2H), 8.48 (dd, J = 3.6, 14.5 Hz, 1H),
10.14 (d, J = 3.6 Hz, 1H), 10.3–10.8 (br, 1H). (Z)-Isomer; 1H
NMR (400 MHz, CDCl3) δ 1.01 (t, J = 7.4 Hz, 3H), 1.76 (tq, J =7.3, 7.4 Hz, 2H), 3.53 (dt, J = 6.8, 7.3 Hz, 2H), 8.48 (d, J =15.3 Hz, 1H), 9.5–9.9 (br, 1H), 10.05 (s, 1H).
4-Aza-5-methyl-2-nitro-2-hexenal (1b)19
Brown solid (E/Z = 76/24). (E)-Isomer; 1H NMR (400 MHz,CDCl3) δ 1.40 (d, J = 6.6 Hz, 6H), 3.75 (sep, J = 6.6 Hz, 1H), 8.52
(ddd, J = 0.6, 3.6, 14.6 Hz, 1H), 10.15 (d, J = 3.6 Hz, 1H),
10.3–10.8 (br, 1H). (Z)-Isomer; 1H NMR (400 MHz, CDCl3)
δ 1.42 (d, J = 6.6 Hz, 6H), 3.84 (sep, J = 6.6 Hz, 2H), 7.95 (d, J =15.4 Hz, 1H), 9.4–9.9 (br, 1H), 10.56 (s, 1H).
4-Aza-5,5-dimethyl-2-nitro-2-hexenal (1c)18
White solid (E/Z = 79/21). (E)-Isomer; 1H NMR (400 MHz,CDCl3) δ 1.45 (s, 9H), 8.57 (dd, J = 3.6, 14.9 Hz, 1H), 10.15 (d,J = 3.6 Hz, 1H), 10.3–10.8 (br, 1H). (Z)-Isomer; 1H NMR(400 MHz, CDCl3) δ 1.47 (s, 9H), 7.99 (d, J = 15.7 Hz, 1H),
9.7–10.1 (br, 1H), 9.94 (s, 1H).
4-Aza-2-nitro-5-phenyl-2-pentenal (1d)White solid; mp 119.2–120.0 °C (E/Z = 77/23). (E)-Isomer; 1H
NMR (400 MHz, CDCl3) δ 4.64 (d, J = 5.9 Hz, 2H), 7.2–7.5 (m,5H), 8.54 (dd, J = 3.6, 14.3 Hz, 1H), 10.16 (d, J = 3.6 Hz, 1H),
10.6–11.0 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 54.5 (CH2),
126.3 (C), 127.8 (CH), 129.1 (CH), 129.5 (CH), 133.9 (CH), 155.0(C), 186.4 (CH). (Z)-Isomer; 1H NMR (400 MHz, CDCl3) δ 4.71
(d, J = 6.0 Hz, 2H), 7.2–7.5 (m, 5H), 7.98 (d, J = 15.1 Hz, 1H),
9.7–10.0 (br, 1H), 10.07 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 54.7 (CH2), 125.1 (C), 127.9 (CH), 129.2 (CH), 129.5 (CH),133.9 (CH), 150.3 (C), 183.4 (CH). HRMS (ESI/TOF) calcd for
C10H10N2O3(M − H+): 205.0619, found: 205.0624; IR (KBr,
cm−1) 3212, 1656, 1606, 1505, 1317.
4-Aza-2-nitro-2,6-pentadienal (1e)5
Yellow oil (E/Z = 78/22). (E)-Isomer; 1H NMR (400 MHz, CDCl3)
δ 4.09 (br dd, J = 5.7, 5.7 Hz, 2H), 5.3–5.5 (m, 2H), 5.90 (ddt, J =5.7, 11.2, 17.0 Hz, 1H), 8.48 (dd, J = 3.6, 14.4 Hz, 1H), 10.15 (d,J = 3.6 Hz, 1H), 10.3–10.8 (br, 1H). (Z)-Isomer; 1H NMRThis journal is © The Royal Society of Chemistry 2020

Brown solid; mp 125.4–126.5 °C (E/Z = 71/29). (E)-Isomer; 1H
NMR (400 MHz, CD3CN) δ 3.1–3.4 (br, 1H), 3.5–3.6 (m, 2H),
3.70 (t, J = 5.2 Hz, 2H), 8.58 (br d, J = 8.8 Hz, 1H), 10.10 (d, J =3.6 Hz, 1H), 10.3–10.7 (br, 1H); 13C NMR (100 MHz, CD3CN)
δ 53.3 (CH2), 60.8 (CH2), 126.8 (C), 157.4 (CH), 186.3 (CH). (Z)Isomer; 1H NMR (400 MHz, CD3CN) δ 3.2–3.4 (br, 1H), 3.62 (t,J = 4.7 Hz, 2H), 3.6–3.8 (m, 2H), 7.96 (d, J = 15.2 Hz, 1H),9.5–9.9 (br, 1H), 9.98 (s, 1H); 13C NMR (100 MHz, CD3CN)
δ 53.4 (CH2), 60.8 (CH2), 125.6 (C), 152.7 (CH), 183.8 (CH).
HRMS (ESI/TOF) calcd for C5H8N2O4(M − H+): 159.0411,
found: 159.0416; IR (KBr, cm−1) 3494, 3216, 1674, 1589, 1491,
1314.
Synthesis of triazabicyclic compounds
To a solution of formylnitroenamine 1a (158.2 mg, 1.0 mmol)
in ethanol (4 mL), ammonium acetate (78.5 mg, 1.0 mmol)
was added, and the resultant mixture was heated at 50 °C for
1 day. After the removal of the solvent under reduced pressure,
the residual brown solid was dissolved in dichloromethane(30 mL) and washed with water (30 mL × 1). The aqueous layer
was extracted with dichloromethane (30 mL × 3). The combined organic layer was dried over magnesium sulfate andevaporated to aﬀord a brown solid as a residue. The solid was
subjected to column chromatography on silica gel using ethyl
acetate/dichloromethane (1/9) as an eluent to aﬀord a mixtureof 2a and 3a as a yellow solid (81.0 mg, 0.27 mmol, 55%) and a
mixture of 3a and 4a as a brown solid (17.9 mg, 0.07 mmol,14%). However, further separation could not be achieved.
When other nitroenamines 1b–f were used, the experiments
were performed in the same way. In the cases of 1b and 1f,
ethyl acetate was used as an extraction solvent instead of dichloromethane. In the case of 1f, ethyl acetate was used as aneluent for column chromatography.
The NMR spectra were analyzed using a mixture of 2 and 3
because these products are interconvertible under equilibrium
when dissolved in solvents. Hence, the content ratio varied ineach measurement. With regard to bicyclic products 3 and 4,
the NMR spectra were measured using a mixture because they
were inseparable despite several attempts. The yields of 3 and
4 were determined on the basis of the integral ratio.
2,6,9-Triaza-4,8-dinitro-2,6-dipropylbicyclo[3.3.1]nona-3,7-diene(2a) and 2,6,9-triaza-4,8-dinitro-2,9-dipropylbicyclo[3.3.1]nona3,7-diene (3a)Yellow solid, mp 152.5–153.3 °C, Rf = 0.43 (SiO2, dichloromethane/methanol = 20/1). 2a; 1H NMR (400 MHz, CDCl3)
δ 0.98 (t, J = 7.4 Hz, 6H), 1.6–1.9 (m, 4H), 2.2–2.3 (br, 1H), 3.43
(ddd, J = 7.7, 7.7, 13.9 Hz, 2H), 3.98 (ddd, J = 5.8, 7.8, 13.9 Hz,
2H), 5.68 (d, J = 2.8 Hz, 2H), 8.20 (s, 2H); 13C NMR (100 MHz,CDCl3) δ 11.1 (CH3), 23.3 (CH2), 56.9 (CH2), 61.9 (CH), 122.4(C), 144.6 (CH). 3a; 1H NMR (400 MHz, CDCl3) δ 0.93 (t, J =Org. Biomol. Chem., 2020, 18, 9109–9116 | 9113

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7.4 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H), 1.56 (ddq, J = 7.2, 7.2,
7.4 Hz, 2H), 1.6–1.9 (m, 2H), 2.37 (dt, J = 7.2, 12.6 Hz, 1H),
2.41 (dt, J = 7.4, 12.6 Hz, 1H), 3.39 (ddd, J = 7.8, 7.8, 14.0 Hz,
1H), 3.95 (ddd, J = 5.4, 8.1, 14.0 Hz, 1H), 5.34 (d, J = 1.4 Hz,
1H), 5.32 (s, 1H), 7.0–7.2 (br, 1H), 8.16 (s, 1H), 8.29 (d, J = 4.7,
1H); 13C NMR (100 MHz, CDCl3) δ 11.1 (CH3), 11.6 (CH3), 20.8
(CH2), 23.2 (CH2), 51.4 (CH2), 56.8 (CH2), 61.3 (CH), 66.9 (CH),122.2 (C), 122.7 (C), 142.2 (CH), 144.4 (CH). HRMS (ESI/TOF)
calcd for C12H19N5O4 (M + H+): 298.1510, found: 298.1515;
IR (KBr, cm−1) 3291, 2965, 1613, 1304, 1226. A single crystal of
2a was obtained as yellow needles by recrystallization from dichloromethane/hexane.
2,6,9-Triaza-4,8-dinitro-2-propylbicyclo[3.3.1]nona-3,7-diene (4a)and 2,6,9-triaza-4,8-dinitro-9-propylbicyclo[3.3.1]nona-3,7-diene(5a)
Yellow solid, mp 91.5–93.6 °C (4a/5a = 89/11). 4a; 1H NMR(400 MHz, CD3CN) δ 0.92 (t, J = 7.4 Hz, 3H), 1.6–1.9 (m, 2H),
2.7–2.9 (br, 1H), 3.45 (ddd, J = 7.7, 7.7, 13.8 Hz, 1H), 3.87 (ddd,
J = 5.5, 7.8, 13.8 Hz, 1H), 5.57 (d, J = 1.6 Hz, 1H), 5.68 (d, J =2.0 Hz, 1H), 7.6–8.1 (br, 1H), 8.20 (s, 1H), 8.22 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 11.1 (CH3), 23.6 (CH2), 55.6 (CH2),
55.7 (CH), 61.5 (CH), 124.0 (C), 124.3 (C), 143.5 (CH), 145.35(CH). 5a; 1H NMR (400 MHz, CD3CN) δ 0.87 (t, J = 7.4 Hz, 3H),
1.51 (ddq, J = 6.7, 6.8, 7.4 Hz, 2H), 2.34 (dt, J = 6.7, 14.7 Hz,
1H), 2.36 (dt, J = 6.8, 14.7 Hz, 1H), 5.33 (s, 2H), 7.6–8.1 (br,2H), 8.22 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 11.7 (CH3), 21.2
(CH2), 51.3 (CH2), 62.0 (CH), 124.0 (C), 142.8 (CH). HRMS (ESI/TOF) calcd for C9H13N5O4 (M − H+): 254.0895, found:
254.0890; IR (KBr, cm−1) 3283, 2965, 1611, 1340, 1225, 1139,
926.
2,6,9-Triaza-2,6-di(2-methylethyl)-4,8-dinitrobicyclo[3.3.1]nona3,7-diene (2b) and 2,6,9-triaza-2,9-di(2-methylethyl)-4,8-dinitrobicyclo[3.3.1]nona-3,7-diene (3b)Yellow solid, mp 160.6–162.1 °C. Signals of 3b were too small
to be assigned. 2b; 1H NMR (400 MHz, CDCl3) δ 1.36 (d, J =6.6 Hz, 12H), 2.1–2.3 (br, 1H), 4.36 (sep, J = 6.6 Hz, 2H), 5.69
(d, J = 2.7 Hz, 2H), 8.27 (s, 2H); 13C NMR (100 MHz, CDCl3)
δ 21.3 (CH3), 24.2 (CH3), 55.5 (CH), 63.4 (CH), 122.7 (C), 140.9(CH); HRMS (ESI/TOF) calcd for C12H18N5O4 (M − H+):
296.1364, found: 296.1375; IR (KBr, cm−1) 3291, 2973, 1609,
1338, 1259, 1230, 1181.
2,6,9-Triaza-2-(2-methylethyl)-4,8-dinitrobicyclo[3.3.1]nona-3,7diene (4b)Brown solid, mp 126.2–127.9 °C. Signals of 5b were too small
to be assigned. 1H NMR (400 MHz, CD3CN) δ 1.30 (d, J =6.6 Hz, 3H), 1.33 (d, J = 6.6 Hz, 3H), 2.7–2.9 (br, 1H), 4.24 (qq,J = 6.6, 6.6 Hz, 1H), 5.57 (d, J = 1.1 Hz, 1H), 5.70 (d, J = 1.2 Hz,
1H), 7.7–8.0 (br, 1H), 8.21 (s, 1H), 8.26 (s, 1H); 13C NMR(100 MHz, CD3CN) δ 21.2 (CH3), 23.9 (CH3), 56.2 (CH), 57.4
(CH), 64.4 (CH), 124.1 (C), 124.9 (C), 141.4 (CH), 143.4 (CH);HRMS (ESI/TOF) calcd for C9H12N5O4 (M − H+): 254.0895,
found: 254.0898; IR (KBr, cm−1) 3283, 1609, 1342, 1232.

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Organic & Biomolecular Chemistry
2,6,9-Triaza-4,8-dinitro[3.3.1]nona-3,7-diene (6)Yellow solid, mp 207.0–208.1 °C (dec.). 1H NMR (400 MHz,DMSO-d6) δ 3.72 (t, J = 2.7 Hz, 1H), 5.51 (d, J = 2.7 Hz, 2H),
8.24 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 56.2 (CH), 123.1(C), 142.8 (CH); HRMS (ESI/TOF) calcd for C6H7N5O4 (M − H+):
212.0425, found: 212.0427; IR (KBr, cm−1) 3166, 3012, 1607,
1353, 1223.
2,6,9-Triaza-2,6-dibenzyl-4,8-dinitrobicyclo[3.3.1]nona-3,7-diene(2d) and 2,6,9-triaza-2,9-dibenzyl-4,8-dinitrobicyclo[3.3.1]nona3,7-diene (3d)Brown solid, mp 155.8–157.5 °C, Rf = 0.29 (SiO2, hexane/ethyl
acetate/triethylamine = 6/4/0.5). 2d; 1H NMR (400 MHz, CDCl3)
δ 1.9–2.1 (br, 1H), 4.68 (d, J = 14.8 Hz, 2H), 5.08 (d, J = 14.8 Hz,
2H), 5.65 (d, J = 2.6 Hz, 2H), 6.9–7.5 (m, 10H), 8.26 (s, 2H). 3d;1
H NMR (400 MHz, CDCl3) δ 3.29 (d, J = 13.4 Hz, 1H), 3.35 (d,J = 13.4 Hz, 1H), 4.63 (d, J = 14.7 Hz, 1H), 4.99 (d, J = 14.7 Hz,
1H), 5.24 (d, J = 1.3 Hz, 1H), 5.35 (d, J = 1.3 Hz, 1H), 6.9–7.5(m, 10H), 8.30 (s, 1H), 8.38 (s, 1H). A signal of N–H wasabsent, which was presumably due to overlapping. The 13C
NMR (100 MHz, CDCl3) measurement was performed using a
mixture of two isomers 2d and 3d. δ 53.7 (CH2), 59.1 (CH2),
59.1 (CH2), 60.7 (CH), 61.1 (CH), 65.8 (CH), 121.8 (C), 122.8(C), 123.0 (C), 128.2 (CH), 128.4 (CH), 128.6 (CH), 128.7 (CH),
128.9 (CH), 129.0 (CH), 129.0 (CH), 129.4 (CH), 129.4 (CH),
134.5 (C), 134.7 (C), 135.0 (C), 142.8 (CH), 144.6 (CH), 144.8(CH); HRMS (ESI/TOF) calcd for C20H19N5O4(M + H+):
394.1510, found: 394.1525; IR (KBr, cm−1) 3279, 3057, 1614,
1318, 1209. A single crystal of 3d was obtained as yellow blocks
by recrystallization from ethanol/diethyl ether.
2,6,9-Triaza-2-benzyl-4,8-dinitrobicyclo[3.3.1]nona-3,7-diene (4d)and 2,6,9-triaza-9-benzyl-4,8-dinitrobicyclo[3.3.1]nona-3,7-diene(5d)
Yellow solid, mp 155.0–155.8 °C. 4d; 1H NMR (400 MHz,
CD3CN) δ 2.6–2.8 (br, 1H), 4.78 (d, J = 15.0 Hz, 1H), 4.99 (d, J =15.0 Hz, 1H), 5.56 (dd, J = 1.0, 2.7 Hz, 1H), 5.63 (d, J = 2.7 Hz,
1H), 7.1–7.5 (m, 5H), 8.24 (s, 1H), 8.26 (s, 1H). 5d; 1H NMR(400 MHz, CD3CN) δ 3.54 (d, J = 13.3 Hz, 1H), 3.59 (d, J =13.3 Hz, 1H), 5.25 (s, 2H), 7.1–7.5 (m, 5H), 8.27 (s, 2H). A
signal of N–H was absent, which was presumably due to overlapping. The 13C NMR (100 MHz, CD3CN) measurement was
performed using a mixture of two isomers 4d and 5d. δ 53.7
(CH2), 57.1 (CH), 58.9 (CH2), 61.5 (CH), 62.5 (CH), 123.8 (C),124.1 (C), 124.9 (C), 128.8 (CH), 129.2 (CH), 129.3 (CH), 129.6(CH), 129.9 (CH), 130.0 (CH), 136.9 (C), 137.4 (C), 142.9 (CH),
143.5 (CH), 145.3 (CH); HRMS (ESI/TOF) calcd for C13H13N5O4(M − H+): 302.0895, found: 302.0895; IR (KBr, cm−1) 3276,
1705, 1610, 1320, 1204, 928.
2,6,9-Triaza-4,8-dinitro-2,6-di(3-propen-1-yl)bicyclo[3.3.1]nona3,7-diene (2e) and 2,6,9-triaza-4,8-dinitro-2,9-di(3-propen-1-yl)
bicyclo[3.3.1]nona-3,7-diene (3e)Brown solid, mp 60.5–62.0 °C. 2e; 1H NMR (400 MHz, CDCl3)
δ 2.20 (br, 1H), 4.17 (dddd, J = 1.5, 1.5, 5.0, 15.4 Hz, 2H), 3.60

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Organic & Biomolecular Chemistry(br dd, J = 7.1, 15.4 Hz, 2H), 5.82 (dddd, J = 1.2, 1.2, 1.2,
17.2 Hz, 2H), 5.3–5.5 (m, 2H), 5.69 (d, J = 2.8 Hz, 2H), 5.87
(dddd, J = 5.0, 7.1, 10.2, 17.2 Hz, 2H), 8.18 (s, 2H). 3e; 1H NMR(400 MHz, CDCl3) δ 3.01 (dddd, J = 1.2, 1.2, 6.4, 13.5 Hz, 1H),
3.08 (dddd, J = 1.2, 1.2, 6.3, 13.5 Hz, 1H), 4.13 (dddd, J = 1.3,
1.3, 5.1, 15.3 Hz, 1H), 4.44 (br dd, J = 7.2, 15.3 Hz, 1H), 5.26
(dddd, J = 1.2, 1.2, 1.2, 17.1 Hz, 1H), 5.29 (dddd, J = 1.3, 1.3,
1.3, 10.2 Hz, 1H), 5.3–5.5 (m, 2H), 5.47 (dddd, J = 1.3, 1.3, 1.3,
17.0 Hz, 1H), 5.34 (d, J = 1.5 Hz, 1H), 5.38 (d, J = 1.5 Hz, 1H),
5.82 (dddd, J = 6.3, 6.4, 10.2, 17.1 Hz, 1H), 5.86 (dddd, J = 5.1,
7.2, 10.2, 17.0 Hz, 1H), 6.2–6.8 (br, 1H), 8.18 (s, 1H), 8.30 (s,1H). The 13C NMR (100 MHz, CDCl3) measurement was performed using a mixture of two isomers 2e and 3e. δ 52.6 (CH2),
57.5 (CH2), 57.5 (CH2), 60.7 (CH), 61.7 (CH), 66.2 (CH), 120.6(CH2), 121.1 (CH2), 121.4 (CH2), 121.8 (C), 122.8 (C), 122.9 (C),131.5 (CH), 131.7 (CH), 132.4 (CH), 142.8 (CH), 144.3 (CH),
144.6 (CH); HRMS (ESI/TOF) calcd for C12H15N5O4 (M − H+):
292.1051, found: 292.1054; IR (KBr, cm−1) 3283, 1613, 1482,
1416, 1309, 920, 760.
2,6,9-Triaza-4,8-dinitro-2-(3-propen-1-yl)bicyclo[3.3.1]nona-3,7diene (4e) and 2,6,9-triaza-4,8-dinitro-9-(3-propen-1-yl)bicyclo[3.3.1]nona-3,7-diene (5e)Yellow solid, mp 135.4–137.5 °C. 4e; 1H NMR (400 MHz,
CD3CN) δ 2.7–2.9 (br, 1H), 4.19 (dddd, J = 1.4, 1.4, 5.0, 15.6 Hz,
1H), 4.43 (dddd, J = 1.4, 1.4, 6.8, 15.6 Hz, 1H), 5.30 (dddd, J =1.4, 1.4, 1.4, 10.2 Hz, 1H), 5.39 (dddd, J = 1.4, 1.4, 1.4, 17.1 Hz,
1H), 5.57 (dd, J = 1.1, 2.7 Hz, 1H), 5.65 (br d, J = 2.8 Hz, 1H),
5.94 (dddd, J = 5.0, 6.9, 10.2, 17.1 Hz, 1H), 7.5–8.1 (br, 1H),
8.18 (s, 1H), 8.22 (s, 1H). 5e; 1H NMR (400 MHz, CD3CN) δ 3.00
(dddd, J = 1.3, 1.3, 6.4, 13.7 Hz, 1H), 3.05 (dddd, J = 1.3, 1.3,
6.4, 13.7 Hz, 1H), 5.30 (dddd, J = 1.3, 1.3, 1.3, 10.2 Hz, 1H),
5.39 (dddd, J = 1.3, 1.3, 1.3, 17.1 Hz, 1H), 5.33 (s, 2H), 5.85
(dddd, J = 6.4, 6.4, 10.2, 17.1 Hz, 1H), 7.5–8.1 (br, 2H), 8.23 (s,2H). The 13C NMR (100 MHz, CD3CN) measurement was performed using a mixture of two isomers 4e and 5e. δ 52.6 (CH2),
57.1 (CH), 57.7 (CH2), 61.5 (CH), 62.8 (CH), 119.9 (CH2), 119.9(CH2), 123.8 (C), 124.1 (C), 124.9 (C), 134.0 (CH), 134.4 (CH),142.8 (CH), 143.4 (CH), 145.1 (CH); HRMS (ESI/TOF) calcd for
C9H11N5O4 (M − H+): 252.0738, found: 252.0740; IR (KBr,
cm−1) 3278, 1610, 1423, 1334, 1215, 927.
2,6,9-Triaza-2,6-di(2-hydroxyethyl)-4,8-dinitro[3.3.1]nona-3,7diene (2f ) and 2,6,9-triaza-2,9-di(2-hydroxyethyl)-4,8-dinitro[3.3.1]nona-3,7-diene (3f )Brown solid, mp 68.1–70.7 °C. 2f; 1H NMR (400 MHz, CD3CN)
δ 2.8–3.0 (br, 1H), 3.0–3.3 (br, 2H), 3.44 (ddd, J = 3.8, 7.0,
14.2 Hz, 2H), 3.69 (ddd, J = 3.8, 6.0, 11.8 Hz, 2H), 3.77 (ddd, J =3.4, 7.0, 11.8 Hz, 2H), 4.01 (ddd, J = 3.4, 6.0, 14.2 Hz, 2H), 5.71
(d, J = 1.0 Hz, 2H), 8.24 (s, 2H); 13C NMR (100 MHz, CD3CN)
δ57.4 (CH2), 61.5 (CH2), 63.3 (CH), 123.5 (C), 144.6 (CH). 3f; 1H
NMR (400 MHz, CD3CN) δ 2.49 (ddd, J = 5.2, 5.2, 13.7 Hz, 1H),
2.64 (ddd, J = 5.0, 5.0, 13.7 Hz, 1H), 2.9–3.1 (br, 1H), 3.0–3.3(br, 1H), 3.5–3.8 (m, 5H, overlapped with signals of 3f ), 3.97
(ddd, J = 3.3, 6.0, 14.7 Hz, 1H), 5.42 (d, J = 1.5 Hz, 1H), 5.61 (d,J = 1.5 Hz, 1H), 7.5–8.2 (br, 1H), 8.26 (s, 1H), 8.27 (s, 1H); 13C

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NMR (100 MHz, CD3CN) δ 51.9 (CH2), 57.3 (CH2), 60.7 (CH2),
61.4 (CH2), 62.1 (CH), 68.4 (CH), 122.9 (C), 123.1 (C), 143.4(CH), 145.9 (CH). HRMS (ESI/TOF) calcd for C10H15N5O6(M − H+): 300.0950, found: 300.0954; IR (KBr, cm−1)1209,
1307, 1612, 2359, 3307.
2,6,9-Triaza-2-(2-hydroxyethyl)-4,8-dinitro[3.3.1]nona-3,7-diene(4f ) and 2,6,9-triaza-9-(2-hydroxyethyl)-4,8-dinitro[3.3.1]nona3,7-diene (5f )Brown solid, mp 95.6–97.2 °C. 4f; 1H NMR (400 MHz, CD3CN)
δ 2.8–3.0 (br, 1H), 2.9–3.4 (br, 1H), 3.57 (ddd, J = 3.8, 6.9,
14.3 Hz, 1H), 3.67 (ddd, J = 3.8, 6.2, 11.6 Hz, 1H), 3.77 (ddd, J =3.5, 6.9, 11.6 Hz, 1H), 3.99 (ddd, J = 3.5, 6.2, 14.3 Hz, 1H), 5.57
(s, 1H), 5.73 (s, 1H), 7.4–8.2 (br, 1H), 8.21 (s, 1H), 8.23 (s, 1H);
13
C NMR (100 MHz, CD3CN) δ 57.0 (CH2), 57.2 (CH), 61.5
(CH2), 63.8 (CH), 124.0 (C), 124.7 (C), 143.5 (CH), 145.6 (CH).
5f; 1H NMR (400 MHz, CD3CN) δ 2.49 (ddd, J = 5.5, 5.5,
13.4 Hz, 1H), 2.55 (ddd, J = 5.1, 5.1, 13.4 Hz, 1H), 2.9–3.4 (br,1H), 3.5–3.7 (m, 2H, overlapped with signals of 4f ), 5.44 (s,2H), 7.4–8.2 (br, 2H), 8.23 (s, 2H); 13C NMR (100 MHz, CD3CN)
δ 51.9 (CH2), 60.7 (CH2), 62.5 (CH), 124.0 (C), 142.7 (CH).
HRMS (ESI/TOF) calcd for C8H11N5O5 (M − H+): 256.0687,
found: 256.0685; IR (KBr, cm−1) 1208, 1226, 1317, 1609, 2359,
3251.
X-Ray crystallographic analysis
Diﬀraction data were collected at 93 or 123 K under a cold N2gas stream using a Rigaku XtaLAB Synergy-S/Mo system (λ =0.71073 Å (Mo-Kα)). The integrated data were analyzed using
the Olex2 crystallographic software package.20 The structures
were solved with the ShelXT structure solution program21
using Intrinsic Phasing and refined with the ShelXL refinement package22 using least-squares minimization. Anisotropic
refinement was performed for all non-hydrogen atoms, and all
the hydrogen atoms were placed at the calculated positions.
Temperature dependent NMR spectra
1

H NMR spectra were obtained by using the variable-temperature (VT) NMR technique. The sample solutions were stored at−10–50 °C for over 12 h prior to the measurements.
Theoretical calculations

Density functional theory (DFT) calculations for 2a, 2d, 3a and3d were conducted using Gaussian 16 W software (revision
A.03)23 using the restricted Becke three-parameter hybrid functionals with the Lee–Yang–Parr correlation (RB3LYP)24,25 and
6-311+G(d,p) basis set.26,27 Ground-state geometries were optimized and, then, the Gibbs energies of the molecules were calculated. Solvation was considered using the conductor-likepolarizable continuum model.28,29

Conﬂicts of interest
There are no conflicts to declare.

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Notes and references
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