Synthesis, structure and thermal decomposition of cycloalkanone enamine peroxides

Article abstract of DOI:10.1016/j.mencom.2009.11.014

Reactions of cycloalkanone enamines with H₂O₂ gave bis(1-morpholinocyclopent-1-yl)- and bis(1-morpholinocyclohex-1-yl)-peroxides, which were studied by NMR spectroscopy and X-ray diffraction. Thermolysis of bis(1-morpholinocyclohex-1-yl)-peroxide in n-hexane resulted in two major products, viz., cyclohexanone and morpholine.

Full text of DOI:10.1016/j.mencom.2009.11.014

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 334–336
Synthesis, structure and thermal decomposition
of cycloalkanone enamine peroxides
Evgenii K. Starostin,a Victor N. Khrustalev,b Mikhail Yu. Antipinb and Andrei V. Lalov*a
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5328; e-mail: land@ioc.ac.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085; e-mail: vkh@xray.ineos.ac.ru
DOI: 10.1016/j.mencom.2009.11.014
Reactions of cycloalkanone enamines with H2O2 gave bis(1-morpholinocyclopent-1-yl)- and bis(1-morpholinocyclohex-1-yl)-
peroxides, which were studied by NMR spectroscopy and X-ray diffraction. Thermolysis of bis(1-morpholinocyclohex-1-yl)-
peroxide in n-hexane resulted in two major products, viz., cyclohexanone and morpholine.
The synthesis and chemical transformations of peroxides are of
considerable interest. However, enamine peroxides were studied
insufficiently. The synthesis of cycloalkanone enamine peroxides
was reported in only one publication,1 but the data provided in
that publication seem unconvincing. The experimentally deter-
mined molecular masses differ by 25–30% from theoretical
values. Almost no data are provided on the chemical trans-
formations of these products.
In this work, we studied the reactions of cycloalkanone
enamines with hydrogen peroxide in order to determine the
structures of the resulting adducts and to explore the thermal
decomposition of the latter.
Reactions of appropriate amines and cycloalkanones in the
presence of p-toluenesulfonic acid with azeotropic removal of
water2 resulted in the following enamines: 1-morpholinocyclo-
pent-1-ene 1a, 1-morpholinocyclohex-1-ene 1b, 1-piperidino-
cyclopent-1-ene 1c, 1-piperidinocyclohex-1-ene 1d and 1-pipe-
ridinocyclohept-1-ene 1e.†
selected geometrical parameters are presented in Figures 1 and 2.
Note that, theoretically, peroxides 2 can have a wide variety
of chemical structures. First, owing to the presence of cyclic
fragments at carbon atoms located in the α-positions with respect
to the peroxide group, the molecules of 2 are chiral and can
†
GLC analyses were carried out on an LKhM-80 chromatograph with a
flame ionization detector using a 3 m×3 mm column with 6% SE-30 on
1
Chromosorb W (60–80 mesh). H and 13C NMR spectra were recorded
on a Bruker AC-200 instrument (200.13 MHz for 1H and 50.32 MHz for
13C). Melting points were determined in sealed capillaries.
The starting ketones and amines of 97–98% purity were purchased
from Acros and Lancaster and used without further purification.
Enamines 1a–e were obtained using a standard procedure2 by boiling
equimolar amounts of the reagents in benzene in the presence of p-toluene-
sulfonic acid with azeotropic removal of water.
Syntheses of peroxides. A starting enamine (0.03 mol) was placed in a
stream of Ar into a flask equipped with a magnetic stirrer, and H2O2
(0.015 mol) was slowly added dropwise as a diethyl ether solution (17 ml);
stirring was continued for another 45 min. The resulting peroxide was
filtered off, washed with anhydrous diethyl ether and recrystallized from
anhydrous diethyl ether at 10 °C.
Reactions of these enamines with aqueous and diethyl ether
H2O2 solutions were studied. The use of aqueous H2O2 resulted
in fast hydrolysis of the starting compounds, whereas the
reaction with the diethyl ether solution allowed us to isolate
individual bis(1-morpholinocyclopent-1-yl)peroxide 2a and bis-
(1-morpholinocyclohex-1-yl)peroxide 2b (Scheme 1),† whose
1-Morpholinocyclopent-1-ene 1a: bp 98 °C (8 Torr). 1H NMR (CDCl3)
d: 1.75–1.95 (m, 2H, CH2), 2.25–2.45 [m, 4H, (CH2)2], 2.80–2.95 [t,
4H, (CH2)2N], 3.60–3.75 [t, 4H, (CH2)2O], 4.35–4.45 (s, 1H, CH=C).
1-Morpholinocyclohex-1-ene 1b: bp 108–109 °C (9 Torr). 1H NMR
(CDCl3) d: 1.45–1.75 (br. m, 4H 2CH2), 1.95–2.15 [m, 4H, (CH2)2],
2.65–2.80 [t, 4H, (CH2)2N], 3.65–3.75 [t, 4H, (CH2)2O], 4.60–4.70 (s,
1H, CH=C).
1
structures were determined by H and 13C NMR spectroscopy
and X-ray diffraction analysis (XRD).
We obtained peroxides 2a and 2b as white crystalline com-
pounds in 80–85% yields; the purity determined by 13C NMR
spectroscopy was 92–93%.
Enamines based on piperidine (1c–e) also react with diethyl
ether H2O2 solutions to give peroxide products; however, we
were unable to isolate them in a pure state as they were
extremely unstable.
The structures of peroxides 2a and 2b were studied by XRD.‡
The general view of the molecules of 2a and 2b along with
1
1-Piperidinocyclopent-1-ene 1c: bp 109 °C (9 Torr). H NMR (CDCl3)
d: 1.40–1.65 (br. m, 6H, 3CH2), 1.75–2.0 (m, 2H, CH2), 2.25–2.45 [m,
4H, (CH2)2], 2.75–2.95 [t, 4H, (CH2)2N], 4.75–4.85 (s, 1H, CH=C).
1
1-Piperidinocyclohex-1-ene 1d: bp 120 °C (9 Torr). H NMR (CDCl3)
d: 1.40–1.75 (br. m, 10H, 5CH2), 1.80–2.00 [m, 4H, (CH2)2], 2.15–2.85
[t, 4H, (CH2)2N], 4.75–4.86 (s, 1H, CH=C).
1-Piperidinocyclohept-1-ene 1e: bp 124 °C (8 Torr). H NMR (CDCl3)
1
d: 1.35–1.72 (br. m, 12H, 6CH2), 2.2–2.35 (m, 4H, 2CH2), 2.55–2.60
[t, 4H, (CH2)2N], 4.72–4.80 (s, 1H, CH=C).
Bis(1-morpholinocyclopent-1-yl)peroxide 2a: bp 84–86 °C. 1H NMR
(CDCl3) d: 2.65–3.00 [br. m, 4H, (CH2)2N], 3.55–3.90 [m, 4H, (CH2)2O].
13C NMR (CDCl3) d: 23.52 (s, CH2CH2), 34.62 (s, CH2–C–CH2), 48.75
(s, CH2N), 67.57 (s, CH2O), 106.25 (s, CON). The product purity is 93%,
according to 13C NMR data.
O
O
N
N
(CH2)n
(CH2)n
H2O2
O
O
O
N
(CH2)n
Bis(1-morpholinocyclohex-1-yl)peroxide 2b: bp 98–99 °C. 1H NMR
(CDCl3) d: 1.4–2.0 (br. m, 10H, 5CH2), 2.70–2.90 [m, 4H, (CH2)2N],
3.60–3.80 [br. m, 4H, (CH2)2O]. 13C NMR (CDCl3) d: 22.18 (CH2),
25.63 (CH2), 29.46 (CH2), 46.01 (CH2N), 67.75 (CH2O), 95.65 (CON).
The product purity is 94%, according to 13C NMR data.
1a n = 0
1b n = 1
2a n = 0
2b n = 1
Scheme 1
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© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 334–336
exist as six different isomers (the conformations of substituents
at carbon atoms located in the α-positions with respect to the
peroxide group are shown):
C(12)
C(11)
C(4A)
C(5A)
C(12A)
C(4)
C(5)
C(13A)
C(3A)
C(3)
C(11A)
C(14A)
C(13)
C(1A)
O(1A)
O(1)
C(1)
N(1)
O(3A)
C(10A)
C(2)
C(10)
C(18)
Two meso-forms: tN/g(C+)-g(C–) – tN/g(C–)-g(C+)
C(2A)
C(6A)
C(14)
N(2)
C(6)
gN(+)/tC-g(C–) – gN(–)/tC-g(C+)
N(1A)
N(2A)
C(18A)
O(3)
C(7A)
C(17)
O(2A)
O(4)
tN/g(C+)-g(C–) – gN(+)/tC-g(C–)
tN/g(C+)-g(C–) – gN(–)/tC-g(C+)
gN(+)/tC-g(C–) – gN(+)/tC-g(C–)
gN(–)/tC-g(C+) – gN(–)/tC-g(C+)
C(7)
Four d,l-forms:
C(9)
C(9A)
C(8A)
C(17A)
C(15A)
C(15)
C(8)
C(16A)
O(4A)
C(16)
O(2)
Figure 1 Molecular structure of 2a; hydrogen atoms are omitted for
clarity; two independent molecules representing the different conformers
are shown. Labels A denote symmetrically equivalent atoms relative to the
2-fold axis. Selected bond lengths (Å) and angles (°): O(1)–O(1A) 1.482(3),
O(3)–O(3A) 1.486(3), O(1)–C(1) 1.459(2), O(3)–C(10) 1.457(2), N(1)–C(1)
1.442(3), N(1)–C(6) 1.469(2), N(1)–C(9) 1.465(3), N(2)–C(10) 1.443(3),
N(2)–C(15) 1.461(3), N(2)–C(18) 1.467(3); O(1A)–O(1)–C(1) 108.1(2),
O(3A)–O(3)–C(10) 108.0(2), N(1)–C(1)–O(1) 114.2(2), N(2)–C(10)–O(3)
114.4(2), O(1)–C(1)–C2 100.6(2), O(1)–C(1)–C(5) 110.3(2), O(3)–C(10)–
C(11) 110.8(2), O(3)–C(10)–C(14) 100.7(2), C(1)–N(1)–C(6) 118.2(2),
C(1)–N(1)–C(9) 114.0(2), C(6)–N(1)–C(9) 109.1(2), C(10)–N(2)–C(15)
114.5(2), C(10)–N(2)–C(18) 117.0(2), C(15)–N(2)–C(18) 109.1(2), C(1)–
O(1)–O(1A)–C(1A) –156.4(2), C(10)–O(3)–O(3A)–C(10A) 158.9(2), O(1A)–
O(1)–C(1)–N(1) –59.1(2), O(3A)–O(3)–C(10)–N(2) –66.6(2), O(1A)–O(1)–
C(1)–C(2) –179.1(1), O(1A)–O(1)–C(1)–C(5) 69.9(2), O(3A)–O(3)–C(10)–
C(11) –63.0(2), O(3A)–O(3)–C(10)–C(14) –172.4(1).
However, the gC-gC conformation of saturated carbon cycles
with respect to the peroxide group is sterically unfavourable;
hence, an experiment is most likely to show the formation of only
three of the isomers specified above, namely, one meso-form
(gN(+)/tC-g(C–) – gN(–)/tC-g(C+)) and two d,l- forms (gN(+)/tC-g(C–)
–
gN(+)/tC-g(–) and gN(–)/tC-g(+) – gN(–)/tC-g(+)). In fact, all the three
isomersCare actually forCmed in compoCunds 2a (both d,l-forms)
and 2b (meso-form). While compound 2a is crystallized as a
racemate of enantiomers of both isomers (space group C2/c),
compound 2b either forms only the meso-form, or its isomers
are spontaneously separated from each other upon crystalliza-
tion (space group P21). The assumption that compound 2b can
exist only as a meso-form follows from the fact that, apparently,
due to steric factors, an increase in the size of cycloalkane sub-
stituents at the carbon atoms in α-positions with respect to the
peroxide group should favour the formation of the meso-form.
Second, isomers of peroxides 2 can also form various con-
formers. Note that the experimentally observed isomers of per-
oxide 2a are different conformers with respect to the orientation
of five-membered rings, which have an envelope conformation
typical of such fragments. In fact, in one of the isomers, it is
the C(4) atom in the β-position to the C(1) nodal carbon atom
which deviates from the plane formed by the other four atoms
in both five-membered rings, whereas in the other isomer, it is
the C(10) nodal atom (Figure 1). In the latter case, the mor-
pholine substituents occupy the equatorial positions, whereas
the peroxide group is axial. Furthermore, the meso-form of
compound 2b observed in a crystal also has an unusual con-
formation with respect to the mutual orientation of the cyclo-
hexane fragments. While one of the cyclohexane fragments
contains a peroxide group in an equatorial position and a
morpholine substituent in an axial position, the other fragment,
conversely, contains a morpholine substituent in an equatorial
position and a peroxide group in an axial position (Figure 2).
Apparently, a superposition of the two geometrical factors
described above gives a single enantiomer of compound 2b;
as a result, crystallization of this compound occurs in chiral
space group P21. It should be noted that both factors can act
independently of each other and can depend on the kinetic
conditions of the reaction.
It is interesting that, despite the different structures of com-
pounds 2a and 2b, the geometric characteristics of their main
peroxide C–O–O–C fragment are rather similar. This fragment
deviates slightly from an ideal planar structure [the torsion
angles are –156.4(2) and 158.9(2)° for 2a and –170.6(3)° for
2b]; this deviation is more significant for compound 2a, as
O(4)
C(18)
C(19)
‡
C(4)
Crystal data for 2a: C18H32N2O4, M = 340.46, monoclinic, space
group C2/c, at 120 K: a = 22.346(3), b = 14.313(2) and c = 15.556(2) Å,
b = 134.008(2)°, V = 3578.5(8) Å3, Z = 8, dcalc = 1.264 g cm–3, F(000) =
= 1488, m = 0.089 mm–1, R1 = 0.059 for 3003 independent reflections
with I > 2s(I), wR2 = 0.177 for all data, GOF = 1.028. 15854 reflections
(3771 unique, Rint = 0.037) were measured on a Bruker SMART 1K
CCD diffractometer (MoKα-radiation, graphite monochromator, j and
w scan mode, 2qmax = 54°).
Crystal data for 2b: C20H36N2O4, M = 368.51, monoclinic, space
group P21, at 100 K: a = 10.7044(14), b = 6.2298(8) and c = 14.517(2) Å,
b = 91.407(3)°, V = 967.8(2) Å3, Z = 2, dcalc = 1.265 g cm–3, F(000) = 404,
m = 0.087 mm–1, R1 = 0.050 for 1469 independent reflections with
I > 2s(I), wR2 = 0.106 for all data, GOF = 1.005. 9706 reflections (2180
unique, Rint = 0.062) were measured on a Bruker SMART 1K CCD
diffractometer (MoKα-radiation, graphite monochromator, j and w scan
mode, 2qmax = 53°).
The structures were determined by direct methods and refined by full-
matrix least squares technique on F2 with anisotropic displacement
parameters for non-hydrogen atoms. The hydrogen atoms were placed in
calculated positions and refined in the riding model with fixed isotropic
displacement parameters. All calculations were carried out using the
SHELXTL program.3
CCDC 745598 and 745599 contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2009.
C(5)
C(17)
C(20)
C(6)
C(3)
C(2)
N(1)
N(2)
O(1)
C(1)
C(8)
C(11)
C(12)
O(2)
C(7)
C(16)
C(10)
C(13)
C(9)
C(15)
C(14)
O(3)
Figure 2 Molecular structure of 2b; hydrogen atoms are omitted for
clarity. Selected bond lengths (Å) and angles (°): O(1)–O(2) 1.497(3),
O(1)–C(1) 1.455(4), O(2)–C(11) 1.458(4), N(1)–C(1) 1.454(4), N(1)–C(7)
1.461(4), N(1)–C(10) 1.473(4), N(2)–C(11) 1.451(4), N(2)–C(17) 1.467(4),
N(2)–C(20) 1.481(5); O(1)–O(2)–C(11) 106.4(2), O(2)–O(1)–C(1) 108.7(2),
N(1)–C(1)–O(1) 113.7(3), N(2)–C(11)–O(2) 114.0(3), O(1)–C(1)–C(2)
111.1(3), O(1)–C(1)–C(6) 101.1(3), O(2)–C(11)–C(12) 111.0(3), O(2)–
C(11)–C(16) 100.6(3), C(1)–N(1)–C(7) 115.6(3), C(1)–N(1)–C(10) 117.2(3),
C(7)–N(1)–C(10) 108.7(3), C(11)–N(2)–C(17) 115.7(3), C(11)–N(2)–C(20)
118.0(3), C(17)–N(2)–C(20) 107.4(3), C(1)–O(1)–O(2)–C(11) –170.6(3),
O(1)–O(2)–C(11)–N(2) 71.2(3), O(2)–O(1)–C(1)–N(1) –77.6(3), O(1)–
O(2)–C(11)–C(12) –56.0(3), O(1)–O(2)–C(11)–C(16) –171.8(2), O(2)–
O(1)–C(1)–C(2) 49.4(3), O(2)–O(1)–C(1)–C(6) 163.6(2).
– 335 –

Mendeleev Commun., 2009, 19, 334–336
one could have expected for d,l-isomers. The O–O bond length
and the O–O–C bond angles have values typical of peroxide
O
O
N
N
molecules with similar structures.4
O
O
2
O
N
Note a structural feature of the compounds studied, namely,
the trans-effect well known for peroxides, which involves
distortion of the tetrahedral coordination of quaternary carbon
atoms bound to oxygen atoms.5 In molecules of 2a and 2b, the
O–C–C bond angles in the trans-position to the O–O peroxide
group decrease in comparison with an ideal tetrahedral angle
of 109.5° down to 100.6(2), 100.7(2) and 101.1(3), 100.6(3)°,
respectively. The six-membered morpholine and cyclohexane
fragments have an almost ideal chair conformation.
In addition to the structures of peroxides 2a and 2b, we also
studied the thermal decomposition of bis(1-morpholinocyclo-
hexyl)peroxide 2b. Thermolysis of a 6% solution of peroxide
2b in n-hexane was carried out at 60 °C in a sealed glass tube
for 6 h until the peroxide decomposed completely.
O
3
+
O
N
O
4
C6H14
O
N
O
NH
4
Scheme 2
References
1 A. Rieche, E. Schmitz and E. Beyr, Chem. Ber., 1959, 92, 1212.
2 S. Hunig and W. Hendle, Chem. Ber., 1960, 93, 909.
3 G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
4 (a) M. Ramm, Z. Kristallogr., 1996, 211, 660; (b) T. S. Balaban,
A. Eichhofer, I. Ghiviriga, H. Hugo and W. Wenzel, J. Org. Chem.,
2003, 68, 5331; (c) K. Nojima, H. Miyamae and Y. Yamaashi, Chem.
Pharm. Bull., 2006, 54, 338.
It was found that cyclohexanone and morpholine were the
main thermolysis products of compound 2b; these products
were formed in 40 and 30% yields, respectively (on a starting
peroxide basis) as determined by GLC with the use of internal
standards.
Based on these data, it can be assumed that the reaction
mechanism involves homolysis of the O–O bond accompanied
by generation of alkoxy radicals 3, which subsequently undergo a
β-decomposition to give cyclohexanone and morpholyl N-radi-
cals 4. The latter abstract a hydrogen atom from the solvent to
give morpholine (Scheme 2).
5 Yu. L. Slovokhotov, T. V. Timofeeva, M. Yu. Antipin and Yu. T. Struchkov,
J. Mol. Struct., 1984, 112, 127.
This homolytic decomposition mechanism of bis(1-mor-
pholinocyclohexyl)peroxide appears most probable; however,
it does not rule out alternative pathways.
Received: 9th April 2009; Com. 09/3319
– 336 –