Products of endic anhydride reaction with cyclic amines and their heterocyclization

Article abstract of DOI:10.1134/S107042800611008X

Products of reaction between bicyclo[2.2.1]hept-5-ene-endo-endo-2,3- dicarboxylic anhydride (endic anhydride) and cyclic amines were obtained. By an example of one of amido acids a conformational analysis was performed and character of hydrogen bonds was

Full text of DOI:10.1134/S107042800611008X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 11, pp. 1642−1652.  Pleiades Publishing, Inc. 2006.
Original Russian Text  L.I. Kas’yan, V.A. Pal’chikov, I.N. Tarabara, O.V. Krishchik, A.O. Kas’yan, S.V. Shishkina, O.V. Shishkin, 2006, published
in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 11, pp. 1655−1665.
Products of Endic Anhydride Reaction with Cyclic Amines
and Their Heterocyclization
L. I. Kas’yana, V.A. Pal’chikova, I. N. Tarabaraa, O. V. Krishchikb,
A. O. Kas’yanc, S. V. Shishkinad, and O. V. Shishkind
aDnepropetrovsk National University, Dnepropetrovsk, 49625 Ukraine
e-mail: cf@ff.dsu.dp.ua
bUkraine State University of Chemical Engineering, Dnepropetrovsk, Ukraine
cInstitute of Organic Chemistry at Rhein-Westfalen Technical University, Aachen, Germany
dResearch and Development Enterprise Single Crystals Institute, Ukrainian Academy of Sciences, Kharkov, Ukraine
Received January 23, 2006
Abstract—Products of reaction between bicyclo[2.2.1]hept-5-ene-endo-endo-2,3-dicarboxylic anhydride (endic
anhydride) and cyclic amines were obtained. By an example of one of amido acids a conformational analysis was
performed and character of hydrogen bonds was studied using quantum-chemical calculations by PM3 procedure.
endo-3-(4-Antipyrylcarbomoyl)-bicyclo[2.2.1]hept-5-ene-endo-2-carboxylic acid with a secondary amide group
was converted into the corresponding carboximide which was epoxidized by performic acid.
DOI: 10.1134/S107042800611008X
7
In contrast to numerous carboximides obtained with
1
the use of bicyclo-[2.2.1]hept-5-ene-endo,endo-2,3-di-
6
2
NHR2
C6H6
O
O
3
carboxilic anhydride (endic anhydride) (I), amido acids
based thereon are hardly studied [1–5]. It is known that
bicyclo[2.2.1]hept-5-ene-endo,endo-2,3-dicarboxylic
acids N-alkylamides were successfully applied as
components of repellent compositions [6] and as agents
endowed with sedative activity [7]. The corresponding
arylamides are present in the composition of a complex
herbicide for cotton plant protection [8], their sodium salts
facilitate the sprouting of plant seeds [9]. The spectral
parameters of amido acids were not reported, The known
amido acids were obtained by heating reagents in alcohol
[10], acetonitrile [11], or tetrahydrofuran [12].
5
4
COOH
NR2
C
O
O
IIa_IIi
I
H3С
(b),
CH3
H3С
(c),
N
NR =
(d),
(a),
N
N
N
N
2
H3C
H3C
(f),
CH3
OH
(e),
N
(g),
O
N
N
O
Ph
(h).
CH3
In this study were investigated endic anhydride
reactions with nonaromatic cyclic amines (pyrrolidine,
piperidine, its 2,6-dimethyl- and 2,2,6,6-tetramethyl
derivatives, hexamethyleneimine, morpholine, piperazine,
and N-hydroxyethylpiperazine). For comparison a reaction
was studied of anhydride I with a primary amine
(aminoantipyrine).
N
N
HN
H3C
HN
NH
O
O
COOH
N
COOH
O
C6H6, 25oC
2
C
C
The reaction of piperazine with a double molar excess
of anhydride I led to the formation of amide IIi containing
two norbornene fragments.
N
O
O
IIi, 67%
1642

PRODUCTS OF ENDICANHYDRIDE REACTION
1643
1
Amido acids IIa–IIh were obtained by reaction of
equimolar amounts of reagents in benzene solution (TLC
monitoring). The synthesis of amido acids IIa, IIb, IIe,
and IIf completed within 24 h, the preparation of
compound IIc required 4 days. We failed to obtain amido
acid IId in the cold, the IR spectrum of the product
contained absorption bands in the region 2650–2510 and
1460–1390 cm–1 indicating the formation of an amine salt
instead of amide. To obtain the latter we were obliged to
boil the reaction mixture for 7 h. The reaction with the
primary amine to synthesize compound IIh proceeded in
the cold for several days.
The structure of amido acids was confirmed by H
and 13C NMR spectra. 1H NMR spectra of amido acids
contain all the expected signals: of olefin protons H5 and
H6 in the region 5.91–6.37 ppm, of bridgehead protons
H1 and H4 in the region 2.92–3.25 ppm, and of protons
H2, H3 close to the carbonyl groups of amido acids (3.10–
3.72 ppm). Protons H2,3 in the spectra of compounds
IIa–IIh are nonequivalent, and to their coupling
correspond vicinal constants 8.1 and 9.6 Hz confirming
the exo-orientation of these protons in the framework.
Closely located bridging protons H7s and H7an (1.14–
1.39 ppm) give signals split by mutual coupling, J 8.0–
8.4 Hz. The high symmetry of the piperazine substituents
in compound IIi should be stressed resulting in super-
position of the respective pairs of signals belonging to
the norbornene framework.
IR spectra of compounds contain absorption bands of
the amide moiety in the regions 1665–1620 (ν CO), 1280–
1250 (ν CN), 3480–3428 cm–1 (ν NH) and of carboxy
group (1745–1720 cm–1). The unsaturated fragment is
revealed by bands in the regions 3076–3054 and 732–
707 cm–1 corresponding to the stretching and bending
vibrations of =C–H bonds respectively [13]. The bands
of stretching vibrations of the strained double bond (1575–
1550 cm–1) are weak and in the spectrum of the
secondary amide IIh they are overlapped by NH group
absorbance [14].
As in 1H NMR spectra, in 13C NMR spectra of amido
acids IIb and IIc a coincidence is observed of signals
from C5 and C6, C1 and C4, C2 and C3, and also of carbonyl
groups signals. In the spectra of the other amido acids
nonequivalent carbon signals from carbonyl groups appear,
and in the spectra of compounds IIa and IIh the carbon
atoms of norbornen framework are nonequivalent.
H
O
+
CH2COOH
C
+
OH
O
+
N
HO
N
m/e 170
F4
m/e 66
F3
M* + 1 (m/e 236)
H+
b
COOH
+
O
CH C C O
HC CH2
H
+
O
H
O
c
O
_C5H5
m/e 65
F5
HC
C C
N
_H2O
N
N
+C
OH
N
O
m/e 54
O
m/e 170
F4
m/e 152
F6
m/e 98
F7
IIa
_CO
H
N
a
+
+
+
C O
m/e 70
O
H
N
F8
O
_CO
N
O
+
m/e 120
F2
O
H
+
C N
O
m/e 217
m/e 92
m/e 218
F1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KAS’YAN et al.
1644
For amido acid IIa we investigated its fragmentation
are capable involthing these sites to transform into other
groups of compounds. By boiling in glacial acetic acid
amido acid IIh was converted into the corresponding
carboxamide IV.
under electron impact. It involves dehydration to form
ion F1, a homolysis of C–C bond leading to fragment ion
F2 (m/e 120) (path a). Path b included in the first stage
a protonation giving ion M* + 1 which suffered a retro-
diene decomposition to F3 (m/e 66) and F4 (m/e 170).
The latter apparently formed also from a nonprotonated
molecule as showed the presence in the mass spectrum
of an ion peak F5 (m/e 65) (path c). Further transforma-
tions of ion F4 include the formation of ions F6 (m/e 152)
and F7 (m/e 98); the latter in its turn is able to fragment
giving ion F8 (m/e 70) resulting from the heterolysis of
the C–N bond.
Imide IV was subjected to epoxidation with performic
acid obtained in situ from 98% formic acid and 50% water
solution of hydrogen peroxide. The successful application
of the performic acid was ensured by its high acidity and
reactivity as an electrophilic oxidative reagent with respect
to substrates containing two electron-withdrawing
substituents that essentially decreased the nucleophilic
reactivity of the olefin. The electron-withdrawing
substituents due to their significant –I-effect prevent
stabilization of cation intermediates and therewith the
opening of the epoxy ring of the formic acid and
occurrence of rearrangements accompanying this process.
Owing just to the substrates structure the hydroxylating
reagent (performic acid) in these reactions shows high
epoxidizing power [16]. In the IR spectra of imide IV
and its epoxy derivative V absorption bands are present
of symmetric and antisymmetric vibrations of the carbonyl
groups in the regions 1758–1735 and 1705–1685 cm–1
[14]. The spectrum of epoxide V contains an absorption
Amido acids contain in their structure conformationally
mobile moieties located in the zone of influence of a bulky
framework, and the conformation of the molecule can
affect the chemical behavior of the reaction sites. For
special attention calls the stabilization of the amido acid
molecule at hydrogen bonds formation, whose energy
was estimated applying semiempirical quantum-chemical
method PM3 [15]. The conformers of amido acid IIb
are distinguished by orientation of the fragments of
carboxy and carboxamide groups with respect to the
norbornene framework. The variation of angles NC8C2C4
and OC9C3C1 allowed a conclusion on the highest
thermodynamic stability of conformer III with an intra-
molecular hydrogen bond between the hydrogen of the
carboxy group and the oxygen from the carboxamide
7
1
6
2
O
COOH
3
5
4
Ph
N
N
C
...
moiety (O–H O=C); the distance of the hydrogen bond
O
N
H
was estimated at 1.770 A. For this structure a character-
istic location of two carbonyl groups in nearly
perpendicular planes was found and spatial removal from
the carbon framework in the equatorial direction of the
nitrogen-containing heterocycle existing in the chair
conformation. Next in stability (difference in heats of
formation equal 2.50 kcal mol−1) was the structure with
CH3
H3C
IIh
7
1
3
6
2
O
Ph
5
O
N
4
no hydrogen bonds; the formation of hydrogen bond O–
AcOH
Boiling
N
...
H
N proved to be less thermodynamically feasible.
N
O
CH3
Hs Han
H3C
IV
H
H
H
H
H
O
H
7
H
H
H
H
1
3
H
N
6
2
O
O
Ph
O
N
O
5
4
H
HCO3H
H H
N
O
H
III
N
O
CH3
Amido acids possess several reactive sites (a strained
H3C
double bond, a carboxy and a carboxamide groups) and
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

PRODUCTS OF ENDICANHYDRIDE REACTION
1645
band characteristic of epoxynorbornanes in the region
858 cm–1 belonging to the stretching vibrations of C–O
bond in the epoxynorbornane fragment [14]. In the IR
spectra of imide IV, epoxide V, as well as of the cor-
responding amido acid IIh the bands are present from
the vibrations of bonds in the heterocyclic fragments.
carried out at 0°C with TLC monitoring in the presence
of a double molar excess of the oxidant (the oxidation of
amido acid IIi was done in a solution of excess performic
acid in formic acid).
Oxidation of amido acids IIb–IIe led to the formation
of two types of compounds: amidolactones IX–XII and
salts XIII–XVI of lactonoacid XVII and the correspond-
ing amines.
Unlike the imides from the norbornene series whose
reactions with organic peracids was freaquently discussed
in special publications [5, 17], oxidation of amido acids
nearly was not investigated formerly. The only instance
was the study of oxidation of an amido acid with a phenyl-
ethyl group whose products were not identified [2].
8
1
2HCO3H, 0oC
(HCO2H)
HO
2
9
6
7
3
CONR2
COOH
NR2
4
5
The oxidation of amido acids may lead both to epoxy
derivatives and to products of their heterocyclization
involving carboxy and amide groups. Events of such
heterocyclization of substituted norbornenes are known,
in particular, lactone VI was obtained on epoxidation of
various bicyclo-[2.2.1]hept-5-ene-2-carboxamides with
the endo-orientation of a substituent under a considerable
excess (4:1) of peracids [18, 19].
O
C
C
O
O
IIb_IIe
IX_XII
HO
HO
_
COO H2+NR2
COOH
O
O
C
C
O
O
XIII_XVI
XVII
7
4
H3C
HO
5
3
RCO3H
2
(IIc, X, XIV),
NR =
(IIb, IX, XIII),
N
N
2
1
6
H3C
O
C
C
O
NHR
CH3
H3C
N
O
VI
(IId, XI, XV),
N
(IIe, XII, XVI).
Amidolactones VII also formed in reaction with
amines (RNH2, R = H, Ph, CH2Ph) of epoxidized endic
anhydride VIII [20]. The reactions occurred under mild
conditions in a weak alkaline medium due to the presence
of amines.
H3C
CH3
The only reaction products of oxidizing amido acids
IIf, IIg, and IIi were salts XVIII–XX.
HO
O
O
_
+
RNH2
O
O
H2N
O
COO
δ
+
C(O)NHR
OH
C6H6, 20oC
_
O
O
C
δ
C
O
O
VIII
XVIII
HO
HO
_
+
OH
H N
N
COO
2
C(O)NHR
O
O
C
O
C
O
XIX
HO
VII
_
+
+
To oxidize the amido acids we chose as in reaction
with imide IV the performic acid obtained in situ from
98% formic acid and 50% water solution of hydrogen
peroxide. Oxidation of amido acids IIb–IIg and IIi was
COO H2N
NH2
O
C
O
2
XX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KAS’YAN et al.
1646
To elucidate the contribution of the nature of the
peracid a reaction of amido acid IIe was performed
with a double excess of peracetic acid obtained in situ
from glacial acetic acid and 50% water solution of
hydrogen peroxide. Reaction was carried out for 10 days
in glacial acetic acid at room temperature with TLC
monitoring. The only reaction product obtained in 71%
yield was salt XVI.
Inasmuch as in experiments on amido acids oxidation
the amidolactones were not the sole products, and the
attempts on chromatographic separation of mixtures of
amidolactones and salts of acid XVII failed we converted
salts XVI and XVIII into amidolactones XII and XXI
by treating with dicyclohexylcarbodiimide (DCC) in
dichloromethane for 3–7 days at room temperature (yields
73 and 80% respectively). The experiments were carried
out with salts of acid XVII with hexamethyleneimine XVI
and morpholine XVIII obtained by oxidation.
Structure ofe endo-9-morpholinocarbonyl-exo-2-hydroxy-4-
oxatricyclo[4.2.1.03,7]nonan-5-one (XXI) according to the data
of X-ray diffraction analysis
group at C2 atom of the bicycloheptane fragment has
exo-orientation, and the substituent attached to C4 atom,
endo-orientation [torsion angles O3C2C3C4 179.4(5)° and
C4C9 –67.4(2)°]. Therewith formed a weak intra-
°
...
...
molecular- hydrogen bond C2–H2 O4 2.37 A (H O
°
...
HO
2.37 A, CH O 119°). The carbonyl group of the sub-
DBU, 20oC
stituent at C4 atom is virtually coplanar with the C3–C4
bond of bicycloheptane fragment [torsion angle
C3C4C9O4 2.5(2)°], and oxazine ring is in ap-conforma-
tion relative to this bond and is so turned that the C13–N1
bond is practically coplanar with C4–C9 bond [torsion
angles C3C4C9N1 –176.1(2)° and C13N1C9C4 6.6(3)°].
This orientation of the oxazine ring results in relatively
strong repulsion between the atoms of the bicycloheptane
O
C N
XVI
(CH2Cl2)
O
C
O
XII
HO
O
O
C N
O
C
fragment and of the heterocycle {shortened
O
XXI
°
...
intramolecular contacts H4 C13 2.79 A (sum of van der
°
...
Waals raddi is 2.87 A [21]), H4 H13a 2.14 A (2.34 A),
°
...
...
H5 H13a 2.20 A (2.34 A), H13a C4 2.47 A (2.87 A),
Using the same dehydrating agent (DCC) we
successfully converted the mixture of 38% of amido-
lactone XII and 62% of salt XVI obtained by oxidation
of amide IIe with performuc acid prepared in situ into
amidol-actone XII in 75% yield. We calculated the
quantity of DCC required for the reaction taking into
account the composition of the mixture determined using
1H NMR spectrum.
°
°
...
H13a C5 2.66 A (2.87 A)}. Apparently, just this steric
strain caused a considerable elongation of C4–C5 bond
[1.580(3) A] as compared to an average value for Csp3
–
°
Csp3 bond 1.542 A [22]. The analysis of bond distances
in the framework compounds of this type showed that
the respective bond always suffered elongation if a sub-
stituent was present at this bond [23–26]. The oxazine
ring exists in the chair conformation (folding parameters
[27]: S 1.16, Θ 1.6°, Ψ 25.2°). Deviations of N1 and O5
atoms from the root-mean-square plane of the other
Structure of compound XXI was proved by X-ray
diffraction analysis (see the figure). The five-membered
heterocycle is present in an envelope conformation.
Deviation of C6 atom from the root-mean-square plane
°
atoms of the ring are –0.63 and 0.64 A respectively.
°
of the other atoms of the ring is –0.60 A . Both five-
In the crystal the molecules of compound XXI form
dimers owing to intermolecular hydrogen bond O3–
membered carbocycles included into the framework
compound are also in the envelope conformation.
Deviation of C7 atom from the root-mean-square plane
of the other atoms for the ring C1–C3, C6, C7 amounts to
...
...
...
HO3 O4' [(–x, –y, 1 – z) H O' 1.86 A, O–H O' 172°]
°
that also assists in elongating O4–C9 bond to 1.240(2) A
°
compared to its average value of 1.210 A. In the crystals
shortened intramolecular contacts were found H1 H11a'
°
...
–0.84 A, and for the ring C3–C7, to 0.84 A. The hydroxy
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

PRODUCTS OF ENDICANHYDRIDE REACTION
1647
°
°
...
(0.5 – x, –0.5 + y, 1.5 – z) 2.19 A (2.34 A), H3 C9' (1 –
H3 (singlet and doublet) unlike in the spectra of the
alternative reaction products. In the spectra of amido-
lactones the singlets of protons H2 are located downfield
whereas in the spectra of lactonoacid XVII salt the more
downfield signal belongs to the doublet of protons H3. In
this fashion we were able to assign signals in the complex
1H NMR spectra and to establish the content of individual
components in the mixtures of oxidation products of amido
acids IIa–IIe.
°
°
...
x, –y, 1 – z) 2.78 A (2.87 A), H5 H7an' (0.5 + x, –0.5 –
y, 0.5 + z) 2.29 A (2.34 A), and H6 C11' (1.5 – x, –0.5 +
°
...
°
y, 1.5 – z) 2.78 A (2.87 A).
The structure of other compounds was studied by IR
1
and H NMR spectroscopy.
The IR spectra of products of amido acids oxidation
contain a broad absorption band in the region 3470–3355
cm–1 [ν(OH)], and also absorption band of two carbonyl
groups, lactone (1795–1770 cm–1) and amide (1640–
1620 cm–1) ones [14]. The stretching vibrations of the
fragment C–O–C included into the five-membered lactone
ring appear as a narrow strong band in the region 1030–
1014 cm–1. A set of bands in the spectra confirms the
presence in the oxidation products of amido acids of
substances with salt character: First of all these are broad
bands or a group of narrow bands in the region 2645–
2480 cm–1 (“ammonium band” of H2N+ group), and also
the bands of antisymmetric and symmetric vibrations of
carboxylate anion in the regions 1640–1590 and 1370–
1348 cm–1. The scissors vibration of the latter gives rise
to a well-defined medium band in the region 775–
760 cm–1 [14].
Amidolactones IX–XII were formed as a result of
a nucleophilic attack of the oxygen from the carboxy
group on the nearest electrophilic carbon of the protonated
epoxy intermediate XXII, and salts of lactonoacid
originate from hydrolysis of iminium intermediate XXIII.
The prevailing formation of salt-like products on
oxidizing compounds IIc and IId compared to compounds
IIb and IIe (82, 95 and 50, 62% respectively) may be
due to the relative stability of intermediate XXIII as
compared to structure XXII caused by electron-donor
effect of the methyl groups.
H
+
O
RCO3H
IIb_IIg, IIi
Analysis of 1H NMR spectra was used for estimating
the number and ratio of components in the oxidation
products of amido acids of the norbornene series.
COOH
NR2
C
O
XXII
1
The H NMR spectra contain signals characteristic
of the products of intramolecular cyclization of compounds
from the norbornene series: a singlet of endo-proton H2
(4.00–5.50 ppm) and a doublet of exo-proton H3 (4.25–
4.70 ppm). The doublet appears because of coupling with
a bridgehead proton H7, whose signal is located in the
region 3.12–3.30 ppm and looks as a complex multiplet
owing to coupling with a large number of nuclei (H8,H6,
H3 etc.). The spectrum of every compound contains also
two doublets from bridging protons (at 1.84–2.15 ppm
HO
H2O
XIII_XVI, XVIII_XX
COOH
+
O
C
NR2
XXIII
In the study of oxidation with performic acid of a large
group of amido acids from the norbornene series including
the rests of heterocyclic nonaromatic amides in the
majority of cases mixtures of substances were obtained
where prevailed the salts of lactonoacid exo-2-hydroxy-
5-oxo-4-[4.2.1.03,7]nonane-9-carboxylic acid with amines
contained in the amido groups of the amido acids .
2
for H8s and 1.38–1.61 ppm for H8an, J8s,8an 10.4–
11.4 Hz) and two signals of exo-protons at C6 and C9
atoms (2.55–2.80 and 2.87–3.09 ppm respectively,
3J6,9 10.4–11.4 Hz), whereas the doublet of each of them
is additionally split by coupling with protons H1 and H7.
The resonances in the region 1.20–3.68 ppm belong to
protons from the substituents attached to the amide
nitrogen.
EXPERIMENTAL
IR spectra were measured on spectrophotometers
UR-20 and Paragon 500 FT-IR from samples pelletized
with KBr. H NMR spectra were registered on
spectrometers Varian VXR (operating frequencies 200
and 300 MHz), Inova 400 (operating frequency 400 MHz),
As criteria for assignment to the oxidation products
of an amidolactone structure or that of a lactonoacid XVII
salt the following spectral features were exploited: proton
signals at the “ammonium” nitrogen atom of salts (8.00–
8.30 ppm) and the reciprocal position of protons H2 and
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KAS’YAN et al.
1648
1
and Gemini-400BB (operating frequency 400 MHz) from
solutions of compounds in DMSO-d6 and CDCl3, internal
reference TMS. 13C NMR spectra were recorded on
spectrometers Inova 400 and Gemini-400BB (operating
frequency 100.57 MHz). Mass spectrum of compound
IIa was measured on AMD Integra 402 instrument at
ionizing electrons energy 70 eV. The monitoring of
reactions progress and checking the purity of compounds
synthesized was carried out by TLC on Silufol UV-254
plates using as eluents ethyl ether (A), ethyl ether–2-
propanol, 1:1 (B), and 2-propanol (C), development in
iodine vapor. Elemental analysis was performed on
analyzer Carlo Erba.
1550, 1254, 1186, 707. H NMR spectrum (200 MHz,
DMSO-d6), δ, ppm: 6.14 m (1H, H6), 6.00 m (1H, H5),
3.41 d.d (1H, H2), 3.23 d.d (1H, H3, J2,3 8.1, J2,1
=
3
3
3J3,4 = 3.3 Hz), 3.00 m (1H, H1), 2.93 m (1H, H4), 1.90–
1.60 (8Hcycle), 1.31 d (1H, H7s), 1.21 d (1H, H7an, 2J7s,7an
8.2 Hz). 13C NMR spectrum (100.57 MHz, DMSO-d6),
δ, ppm: 173.4 (C=O), 170.2 (C=O), 136.2 (C6), 133.3
(C5), 48.4 (C2), 48.0 (C7), 47.6 (C3), 46.1 (C1), 46.0 (C4),
45.8, 45.5, 25.8, 24.0 (Ccycle). Found, %: C 66.35; H 7.21;
N 6.01. C13H17NO3. Calculated, %: C 66.38; H 7.23;
N 5.96.
endo-3-(piperidinocarbonyl)bicyclo[2.2.1]-hept-
5-ene-endo-2-carboxylic acid (IIb). Yield 4.94 g (99%),
mp 133–135°C, Rf 0.59 (A). IR spectrum, cm–1: 3445,
3070, 1735, 1640, 1570, 1260, 1175, 725. 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 6.08 m (2H,
H5, H6), 3.14 m (2H, H2, H3), 3.00, 1.64, 1.56 (10Hcycle),
Crystals of compound XXI monoclinic. C13H17NO5.
°
At –173°C a 6.080(2), b 16.849(3), c 11.481(2) A,
°
β 100.14(2)°, V 1157.8(4) A3, Mr 267.28, Z 4, space group
P21/n, dcalc 1.551 g/cm3, µ(MoKα) 0.119 mm–1, F(000)
580. Parameters of the unit cell and intensity of
5894 reflections (2635 independent, Rint 0.055) were
measured on a diffractometer Xcalibur-3 (MoKα radiation,
CCD-detector, graphite monochromator, ω-scanning,
2θmax 55°).
2.98 m (2H, H1, H4), 1.24 d (1H, H7s), 1.14 d (1H, H7an
,
2J7s,7an 8.0 Hz). 13C NMR spectrum (100.57 MHz,
DMSO-d6), δ, ppm: 176.3 (C=O), 136.1 (C5, C6), 49.4
(C2, C3), 49.1 (C1, C4), 47.3 (C7), 44.5, 23.1, 22.6 (Ccycle).
Found, %: C 67.49; H 7.60; N 5.65. C14H19NO3.
Calculated, %: C 67.47; H 7.63; N 5.62.
The structure was solved by the direct method using
software SHELXTL [28]. Hydrogen atoms positions
were revealed from the difference synthesis of the
electron density and were refined isotropically. The
structure was refined by F2 full-matrix least-mean-
squares procedure in anisotropic approximation for
nonhydrogen atoms till wR2 0.136 by 2614 reflexions [R1
0.056 by 1744 reflexions with F > 4σ(F), S 0.950]. The
crystallographic data, atom coordinates, and geometric
parameters of the structure are deposited in the
Cambridge Structural Database (structure no. 293682).
endo-3-(2,6-Dimethylpiperidinocarbonyl)-
bicyclo[2.2.1]hept-5-ene-endo-2-carboxylic acid
(IIc). Yield 4.28 g (77%), mp 116–118°C, Rf 0.19 (A) Rf
0.39 (Β). IR spectrum, cm–1: 3430, 3065, 1720, 1635,
1
1560, 1270, 1180, 730. H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 6.03 m (2H, H5, H6), 3.10 m (2H,
H2, H3), 3.03–2.96, 1.74–1.66, 1.46–1.36 (8Hcycle),
2.94 m (2H, H1, H4), 1.27 d (1H, H7s), 1.19 d (1H, H7an
,
2J7s,7an 8.0 Hz), 1.15 s (3H, CH3), 1.14 s (3H, CH3).
13C NMR spectrum (100.57 MHz, DMSO-d6), δ, ppm:
176.2 (C=O), 136.1 (C5, C6), 53.0, 23.0, 20.0 (Ccycle), 49.4
(C2, C3), 49.1 (C1, C4), 47.3 (C7), 30.7 (CH3). Found, %:
C 69.21; H 8.36; N 5.11. C16H23NO3. Calculated, %:
C 69.31; H 8.30; N 5.05.
Reaction of bicyclo[2.2.1]-hept-5-ene-endo,endo-
2,3-dicarboxylic anhydride (I) with cyclic amines.
To 3.28 g (0.02 mol) of endic anhydride (I) in 20–25 ml
of benzene was added at stirring 0.02 mol of an
appropriate amine. The reaction mixture was stirred at
room temperature till completion of the reaction (TLC
monitoring), usually from 1 to 4 days. The precipitated
crystals were filtered off, washed with benzene on the
filter, and dried in air. The reaction products were
additionally purified by recrystallization from benzene or
2-propanol. By this procedures were synthesized amido
acids IIa–IIc, and IIe–IIi.
endo-3-(1-Azepanylcarbonyl)bicyclo[2.2.1]hept-
5-ene-endo-2-carboxylic acid (IIe). Yield 4.38 g (83%),
mp 109–111°C, Rf 0 (at start) (A), 0.32 (B). IR spectrum,
cm–1: 3440, 3075, 1730, 1620, 1550, 1275, 1185, 715.
1H NMR spectrum (300 MHz, DMSO-d6), δ, ppm:
6.08 m (2H, H5, H6), 3.11 m (2H, H2, H3), 3.05, 1.73,
1.58 (12Hcycle), 3.03 m (2H, H1, H4), 1.24 d (1H, H7s),
1.15 d (1H, H7an, 2J7s,7an 8.0 Hz). Found, %: C 68.39; H
8.01; N 5.29. C15H21NO3. Calculated, %: C 68.44; H
7.98; N 5.32.
endo-3-(Tetrahydro-1H-pyrrolylcarbonyl)-
bicyclo[2.2.1]hept-5-ene-endo-2-carboxylic acid
(IIa). Yield 3.71 g (79%), mp 168–170°C, Rf 0.11 (A),
0.67 (C). IR spectrum, cm–1: 3436, 3063, 1724, 1640, 1594,
endo-3-(Morpholinocarbonyl)bicyclo[2.2.1]-hept-
5-ene-endo-2-carboxylic acid (IIf). Yield 4.65 g (93%),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

PRODUCTS OF ENDICANHYDRIDE REACTION
1649
mp 148–150°C, Rf 0.69 (C). IR spectrum, cm–1: 3430,
3060, 1730, 1635, 1560, 1280, 1190, 715. H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 6.30 m (1H,
H6), 5.92 m (1H, H5), 3.60–3.55 (8Hcycle), 3.48 m (2H,
H2, H3), 3.11 m (1H, H1), 2.92 m (1H, H4), 1.31 m (2H,
H7s, H7an). Found, %: C 62.18; H 6.82; N 5.54.
C13H17NO4. Calculated, %: C 62.15; H 6.77; N 5.58.
endo-3-(2,2,6,6-Tetramethyl-1-piperidino-
carbonyl)bicyclo[2.2.1]hept-5-ene-endo-2-
carboxylic acid (IId). To 3.28 g (0.02 mol) of endic
anhydride (I) in 25 ml of anhydrous benzene was added
2.82 g (0.02 mol) of 2,2,6,6-tetramethylpiperidine, and the
mixture was boiled for 7 h (TLC monitoring). On cooling
the precipitated crystals were filtered off, washed with
benzene on the filter, dried in air, and purified by
recrystallization from a mixture benzene–2-propanol, 1:1.
Yield 4.12 g (68%), mp 124–126°C, Rf 0.12 (B), 0.20
(C). IR spectrum, cm–1: 3430, 3054, 1728, 1622, 1578,
1272, 1184, 732. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 6.26 m (1H, H6), 6.07 m (1H, H5), 3.72 m
(1H, H2), 3.34 m (1H, H3), 3.12 m (1H, H1), 3.00 m (1H,
H4), 1.65–1.53 (6H, 3CH2), 1.33 (12H, 4CH3), 1.24 d
(1H, H7s), 1.14 d (1H, H7an, 2J7s,7an 8.0 Hz). Found, %:
C 70.73; H 8.81; N 4.63. C18H27NO3. Calculated, %: C
70.82; H 8.85; N 4.59.
1
endo-3-[4-(2-Hydroxyethyl)piperazino-
carbonyl]bicyclo[2.2.1]hept-5-ene-endo-2-
carboxylic acid (IIg). Yield 4.94 g (84%), mp 187–
189°C, Rf 0.02 (C). IR spectrum, cm–1: 3460, 3275, 3075,
1
1665, 1430, 1265, 725. H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 6.26 d.d (1H, H6), 5.91 d.d (1H, H5,
3J5,6 5.4, 3J6,1 = 3J5,4 = 2.7 Hz), 4.25 br.s (1H, OH), 3.65
m (1H, H2), 3.60 m (1H, H3), 3.50 t (2H, CH2), 3.25 m
(2H, H1, H4), 3.10–2.95, 2.60–2.20 (8Hcycle), 2.45 t (2H,
CH2), 1.30 m (2H, H7s, H7an). Found, %: C 61.18;
H 7.39; N 9.41. C15H22N2O4. Calculated, %: C 61.22;
H 7.48; N 9.52.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-
1H-4-pyrazolyl)bicyclo[2.2.1]hept-5-ene-endo,endo-
2,3-dicarboximide (IV). To 15 ml of glacial acetic acid
was added 0.73 g (2 mmol) of amido acid IIh, and the
mixture obtained was boiled till completion of reaction
(TLC monitoring). The acetic acid was distilled off in a
vacuum, to the solid residue 7 ml of ice water was added,
the separated crystals were filtered off, dried, and
recrystallized from 2-propanol. Yield 0.51 g (74%),
mp 232.5–234°C, Rf 0 (at start) (A), 0.28 (B), 0.43 (C).
IR spectrum, cm–1: 3060, 1758, 1705, 1662, 1588, 1487,
endo-3-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-di-
hydro-1H-4-pyrazolylcarbamoyl)bicyclo[2.2.1]-
hept-5-ene-endo-2-carboxylic acid (IIh). Yield 6.28 g
(86%), mp 228–230°C, Rf 0.52 (C). IR spectrum, cm–1:
1
3480, 3060, 1745, 1620, 1260, 1159, 708. H NMR
spectrum (400 MHz, CDCl3), δ, ppm: 8.76 br.s (1H, NH),
7.43–7.24 (5Harom), 6.37 d.d (1H, H6), 6.15 d.d (1H, H5,
3J6,1 = 3J5,4 = 2.8 Hz), 3.48 d.d (1H, H2), 3.35 d.d (1H,
H3, 3J2,3 9.6, 3J3,4 3.2 Hz), 3.10 m (1H, H1), 3.03 C (3H,
CH3), 3.01 m (1H, H4), 2.04 s (3H, CH3), 1.39 d (1H,
1
1185, 848, 715. H NMR spectrum (300 MHz, DMSO-
2
H7s), 1.28 d (1H, H7an, J7s,7an 8.4 Hz). 13C NMR
d6), δ, ppm: 7.39–7.31 (5Harom), 6.26 m (2H, H5, H6),
3.57 m (1H, H1), 3.51 m (1H, H4), 3.43 m (2H, H2, H3),
3.15 s (3H, CH3), 2.08 s (3H, CH3), 1.61 m (2H, H7s,
H7an). Found, %: C 68.71; H 5.50; N 12.11. C20H19N3O3.
Calculated, %: C 68.77; H 5.44; N 12.03.
spectrum (100.57 MHz, CDCl3), δ, ppm: 175.6 (C=O),
172.9 (C=O), 161.9 (C=O), 136.6 (C6), 135.6 (C5), 135.2–
127.6 (Carom), 49.0 (C2), 48.9 (C7), 48.1 (C3), 46.3 (C1),
46.0 (C4), 45.5, 45.0 (Ccycle), 35.6 (CH3), 11.7 (CH3).
Found, %: C 65.43; H 5.76; N 11.39. C20H21N3O4.
Calculated, %: C 65.40; H 5.72; N 11.44.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-
1H-4-pyrazolyl)-exo-5,6-epoxybicyclo[2.2.1]-
heptane-endo,endo-2,3-dicarboxamide (V). To 0.70 g
(2 mmol) of compound IV in 6–7 ml of 98% formic acid
was added dropwise at stirring 0.23 ml (4 mmol) of 50%
water solution of hydrogen peroxide, and the stirring was
continued at room temperature till the end of the reaction
(TLC monitoring). The volatile substances were removed
in a vacuum, to the solid residue 5–7 ml of ice water was
added, the separated crystals were filtered off, dried, and
recrystallized from 2-propanol. Yield 0.49 g (67%), mp
243–245°C, Rf 0 (at start) (A), Rf 0.32 (C). IR spectrum,
cm–1: 3030, 1735, 1685, 1615, 1510, 1400, 1188, 858.
1H NMR spectrum (300 MHz, DMSO-d6), δ, ppm: 7.55–
N,N'-{Di(endo-2-carboxybicyclo[2.2.1]hept-5-
ene-endo-3-carbonyl)}piperazine (IIi) was prepared
from 0.02 mol of anhydride I and 0.01 mol of piperazine.
Yield 5.52 g (67%), mp 214–216°C (decomp.), Rf 0.75
(C). IR spectrum, cm–1: 3428, 3076, 1728, 1620, 1574,
1
1254, 1224, 1174, 720. H NMR spectrum (300 MHz,
DMSO-d6), δ, ppm: 6.27 m (2H, H6), 5.92 m (2H, H5),
3.37 m (2H, H2), 3.33 m (2H, H3), 3.68–3.65, 2.91–2.89
(8Hcycle), 3.07 m (4H, H1, H4), 1.34 d (2H, H7s), 1.30 d
(2H, H7an, 2J7s,7an 8.1 Hz). Found, %: C 63.71; H 6.33;
N 6.81. C22H26N2O6. Calculated, %: C 63.77; H 6.28;
N 6.76.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KAS’YAN et al.
1650
7.48 (5Harom), 3.36 m (1H, H5), 3.31 m (1H, H6), 3.19 s
(3H, CH3), 2.96 m (2H, H2, H3), 2.91 m (2H, H1, H4),
1.77–1.65 (6H, 3CH2), 1.47 d (1H, H8an, 2J8s,8an 11.0 Hz),
1.36–1.33 (2H, 2CH), 1.20 (6H, 2CH3).
2.17 s (3H, CH3), 1.37 d (1H, H7s), 1.10 d (1H, H7an
,
Mixture of endo-9-(2,2,6,6-tetramethyl-1-
piperidino)carbonyl-exo-2-hydroxy-4-oxatri-
cyclo[4.2.1.03,7]nonan-5-one (XI) (5%) and 2,2,6,6-
tetramethylpiperidinium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]-nonane-endo-9-carboxylate
(XV) (95%). Yield 0.56 g (86%). IR spectrum, cm–1:
3435, 2620, 2480, 1775, 1635, 1595, 1395, 1360, 1175,
1025, 770. 1H NMR spectrum (200 MHz, DMSO-d6), δ,
ppm (XI): 5.28 s (1H, H2), 5.10 br.s (1H, OH), 4.56 d
(1H, H3, 3J3,7 4.8 Hz), 3.28 m (1H, H7), 3.07 d.d (1H, H9,
3J9,1 3.0, 3J6,9 10.6 Hz), 2.73 d.d (1H, H6, 3J6,7 4.2 Hz),
2.39 br.s (1H, H1), 1.86 d (1H, H8s), 1.66–1.51 (6Hcycle),
2J7s,7an 10.2 Hz). Found, %: C 65.71; H 5.30; N 11.46.
C20H19N3O4. Calculated, %: C 65.75; H 5.21; N 11.51.
Oxidation of amido acids of norbornene series
with performic acid in situ. To 2 mmol of an appropriate
amido acid IIb–IIg and IIi in 5–8 ml of 98% formic
acid was added dropwise at 0°C while stirring 0.23 ml
(4 mmol) of 50% water solution of hydrogen peroxide,
and the stirring was continued at this temperature till the
end of the reaction (TLC monitoring). The formic acid
was removed in a vacuum, to the oily residue was added
ethyl ether, and after prolonged grinding in the cold the
formed crystals were filtered off and dried.
2
1.45 d (1H, H8an, J8s,8an 10.4 Hz), 1.33 (12H, 4CH3);
(XV): 8.24 br.s (2H, H2N+), 5.10 br.s (1H, OH), 4.29 d
(1H, H3, 3J3,7 5.6 Hz), 4.02 s (1H, H2), 3.17 m (1H, H7),
3.00 d.d (1H, H9, 3J9,1 3.3, 3J6,9 10.9 Hz), 2.62 d.d (1H,
Mixture of endo-9-(piperidino)carbonyl-exo-2-
hydroxy-4-oxatricyclo-[4.2.1.03,7]-nonan-5-one (IX)
(50%) and piperidinium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]-nonane-endo-9-carboxylate
(XIII) (50%). Yield 0.42 g (76%). IR spectrum, cm–1:
3400, 2555, 1770, 1625, 1595, 1400, 1355, 1170, 1030,
3
H6, J6,7 5.0 Hz), 2.39 br.s (1H, H1), 1.94 d (1H, H8s),
1.66–1.51 (6Hcycle), 1.48 d (1H, H8an, 2J8s,8an 10.4 Hz),
1.33 (12H, 4CH3).
1
770. H NMR spectrum (300 MHz, DMSO-d6), δ, ppm
Mixture of endo-9-(1-azepanyl)carbonyl-exo-2-
hydroxy-4-oxatricyclo-[4.2.1.03,7]-nonan-5-one (XII)
(38%) and azepanium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]-nonane-endo-9-carboxylate
(XVI) (62%). Yield 0.21 g (36%). IR spectrum, cm-1:
3600, 3460, 2600, 1790, 1740, 1640, 1415, 1355, 1200,
(IX): 4.80 br.s (1H, OH), 4.75 C (1H, H2), 4.70 d (1H,
3
H3, J3,7 5.1 Hz), 3.27 m (1H, H7), 3.04 d.d (1H, H9,
3J6,9 10.8 Hz), 2.61 d.d (1H, H6, 3J6,7 4.5 Hz), 2.36 br.s
(1H, H1), 1.98 d (1H, H8s), 1.64, 1.53 (10Hcycle), 1.53 d
(1H, H8an, 2J8s,8an 11.1 Hz); (XIII): 8.15 br.s (2H, H2N+),
4.25 d (1H, H3, 3J3,7 5.7 Hz), 4.12 C (1H, H2), 3.37 br.s
(1H, OH), 3.12 m (1H, H7), 2.87 d.d (1H, H9, 3J9,1 3.9,
3J6,9 11.4 Hz), 2.55 d.d (1H, H6, 3J6,7 5.4 Hz), 2.36 br.s
(1H, H1), 1.90 d (1H, H8s), 1.64, 1.53 (10Hcycle), 1.43 d
(1H, H8an, 2J8s,8an 10.8 Hz).
1
1180, 1030, 770. H NMR spectrum (300 MHz, CDCl3),
δ, ppm (XII): 6.49 br.s (1H, OH), 5.50 C (1H, H2),
4.57 d (1H, H3, 3J3,7 5.1 Hz), 3.30 m (1H, H7), 3.09 d.d
3
(1H, H9, 3J9,1 3.8, J6,9 10.7 Hz), 2.80 d.d (1H, H6,
3J6,7 3.8 Hz), 2.15 d (1H, H8s), 2.02 br.s (1H, H1), 1.88,
1.72–1.68 (12Hcycle), 1.59 d (1H, H8an, 2J8s,8an 11.3 Hz);
(XVI): 8.03 br.s (2H, H2N+), 6.49 br.s (1H, OH), 4.50 d
(1H, H3, 3J3,7 5.1 Hz), 4.29 C (1H, H2), 3.22 m (1H, H7),
3.05 d.d (1H, H9, 3J9,1 3.0, 3J6,9 10.8 Hz), 2.70 d.d (1H,
Mixture of endo-9-(2,6-dimethyl-1-piperidino)-
carbonyl-exo-2-hydroxy-4-oxatricyclo[4.2.1.03,7]-
nonan-5-one (X) (18%) and 2,6-dimethylpiperidinium
exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]-
nonane-endo-9-carboxylate (XIV) (82%). Yield
0.48 g (81%). IR spectrum, cm–1: 3355, 2570, 1770, 1620,
1590, 1390, 1355, 1170, 1025, 770. 1H NMR spectrum
(200 MHz, DMSO-d6), δ, ppm (X): 5.33 C (1H, H2),
5.10 br.s (1H, OH), 4.54 d (1H, H3, 3J3,7 5.0 Hz), 3.25 m
3
H6, J6,7 4.1 Hz), 2.06 br.s (1H, H1), 1.88, 1.72–1.68
1
(12Hcycle). H NMR spectrum (300 MHz, DMSO-d6)
(XII): 6.70 br.s (1H, OH), 5.37 C (1H, H2), 4.53 d (1H,
H3, 3J3,7 4.8 Hz), 3.24 m (1H, H7), 1.78–1.68, 1.60–1.56
(12Hcycle), 3.00 d.d (1H, H9, 3J6,9 10.5 Hz), 2.66 d.d (1H,
3
(1H, H7), 3.05 d.d (1H, H9, 3J9,1 3.6, J6,9 10.4 Hz),
3
H6, J6,7 4.2 Hz), 2.38 br.s (1H, H1), 1.84 d (1H, H8s),
2.68 d.d (1H, H6, 3J6,7 4.4 Hz), 2.39 br.s (1H, H1), 1.84 d
1.61 d (1H, H8an, 2J8s,8an 11.1 Hz); (XVI): 8.20 br.s (2H,
H2N+), 6.70 br.s (1H, OH), 4.27 d (1H, H3, 3J3,7 5.1 Hz),
4.07 C (1H, H2), 3.15 m (1H, H7), 2.95 d.d (1H, H9,
3J9,1 3.3, 3J6,9 10.5 Hz), 2.59 d.d (1H, H6, 3J6,7 4.2 Hz),
2.38 br.s (1H, H1), 1.92 d (1H, H8s), 1.78–1.68, 1.60–
1.56 (12Hcycle), 1.46 d (1H, H8an, 2J8s,8an 10.5 Hz).
(1H, H8s), 1.77–1.65 (6H, 3CH2), 1.38 d (1H, H8an
,
2J8s,8an 11.0 Hz), 1.36–1.33 (2H, 2CH), 1.20 (6H, 2CH3);
(XIV): 8.30 br.s (2H, H2N+), 5.10 br.s (1H, OH), 4.28 d
(1H, H3, 3J3,7 4.8 Hz), 4.04 s (1H, H2), 3.16 m (1H, H7),
2.97 d.d (1H, H9, 3J9,1 3.6, 3J6,9 11.2 Hz), 2.60 d.d (1H,
3
H6, J6,7 4.5 Hz), 2.39 br.s (1H, H1), 1.93 d (1H, H8s),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

PRODUCTS OF ENDICANHYDRIDE REACTION
1651
Morpholinium exo-2-hydroxy-5-oxo-4-oxatri-
cyclo[4.2.1.03,7]-nonane-endo-9-carboxylate
(XVIII). Yield 0.45 g (80%), mp 174–177°C. IR
spectrum, cm–1: 3410, 2530, 1785, 1595, 1410, 1360, 1170,
1120, 1025, 765. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 8.02 br.s (2H, H2N+), 4.29 d (1H, H3,
3J3,7 5.0 Hz), 4.05 s (1H, H2), 3.70 br.s (1H, OH), 3.60–
3.50, 3.40–3.34 (8Hcycle), 3.16 m (1H, H7), 2.98 d.d (1H,
H9, J9,1 3.5, J6,9 10.7 Hz), 2.61 d.d (1H, H6,
3J6,7 4.5 Hz), 2.39 br.s (1H, H1), 1.93 d (1H, H8s), 1.48 d
(1H, H8an, 2J8s,8an 10.7 Hz). Found, %: C 54.69; H 6.60;
N 4.96. C13H19NO6. Calculated, %: C 54.74; H 6.67;
N 4.91.
prolonged grinding in the cold the formed crystals were
filtered off and dried. Yield 0.42 g (71%), mp 151–153°C.
IR spectrum, cm–1: 3470, 2600, 1795, 1725, 1610, 1420,
1
1370, 1170, 1030, 770. H NMR spectrum (300 MHz,
DMSO-d6), δ, ppm: 8.00 br.s (2H, H2N+), 4.27 d (1H,
H3, 3J3,7 5.1 Hz), 4.08 s (1H, H2), 3.15 m (1H, H7), 2.93
3
3
d.d (1H, H9, J9,1 3.2, J6,9 10.7 Hz), 2.58 d.d (1H, H6,
3J6,7 4.4 Hz), 2.38 br.s (1H, H1), 1.92 d (1H, H8s), 1.73,
1.58 (12Hcycle), 1.46 d (1H, H8an, 2J8s,8an 11.4 Hz). Found,
%: C 60.69; H 7.80; N 4.63. C15H23NO5. Calculated, %:
C 60.61; H 7.74; N 4.71.
3
3
Substituted endo-9-carbamoyl-exo-2-hydroxy-4-
oxatricyclo[4.2.1.03,7]nonan-5-ones XII and XXI. To
2 mmol of salt XVI or XVIII in 10–12 ml of anhydrous
dichloromethane was added at room temperature while
stirring a solution of 0.41 g (2 mmol) of dicyclohexyl-
carbodiimide in 5 ml of anhydrous dichloromethane.After
stirring for 4–7 days the precipitate was filtered off and
washed on the filter with dichloromethane. The filtrate
was evaporated in a vacuum, the solid residue was ground
under a layer of ethyl ether, the reaction product was
filtered off, washed with ether, and dried in air. The solid
dicyclohexylurea was stirred with 12–15 ml of water for
40 min at 40–45°C, insoluble in water dicyclohexylurea
was filtered off and washed with water. The water filtrate
was evaporated till solid residue was obtained. Both
portions of the product were combined and thrice
recrystallized from 2-propanola (or acetone).
1-(2-Hydroxyethyl)-4-piperazinium exo-2-
hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-
endo-9-carboxylate (XIX). Yield 0.52 g (79%), oily
substance. IR spectrum, cm–1: 3400, 2645, 1787, 1732,
1
1605, 1415, 1365, 1215, 1185, 1030, 775. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 8.02 br.s (2H,
3
H2N+), 4.30 d (1H, H3, J3,7 4.5 Hz), 4.03 s (1H, H2),
3.51 t (2H, CH2), 3.36, 2.41 (8Hcycle), 3.18 m (1H, H7),
3.01 d.d (1H, H9, 3J9,1 2.7, 3J6,9 10.5 Hz), 2.64 d.d (1H,
3
H6, J6,7 4.2 Hz), 2.43 br.s (1H, H1), 2.35 t (2H, CH2),
2
1.94 d (1H, H8s), 1.50 d (1H, H8an, J8s,8an 10.5 Hz).
Found, %: C 54.83; H 7.39; N 8.63. C15H24N2O6.
Calculated, %: C 54.88; H 7.32; N 8.54.
Piperazinium exo-2-hydroxy-5-oxo-4-oxatri-
cyclo[4.2.1.03,7]nonane-endo-9-carboxylate (XX) was
obtained by treating with 8 mmol of oxidant 2 mmol of
amide IIi. Yield 0.34 g (59%), mp 170–172°C. IR
spectrum, cm–1: 3400, 2606, 1782, 1632, 1414, 1348, 1202,
1178, 1014, 760. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 8.21 br.s (2H, H2N+), 8.00 br.s (2H, H2N+),
5.25 br.s (2H, OH), 4.27 d (2H, H3, 3J3,7 4.8 Hz), 4.00 s
(2H, H2), 3.54–3.50, 3.40–3.30 (8Hcycle), 3.15 m (2H, H7),
2.98 d.d (2H, H9, 3J9,1 3.6, 3J6,9 11.0 Hz), 2.61 d.d (2H,
endo-9-1-Azepanylcarbonyl-exo-2-hydroxy-4-
oxatricyclo[4.2.1.03,7]nonan-5-one (XII). Yield
0.41 g (73%), mp 230–231°C, Rf 0.65 (C). IR spectrum,
1
cm–1: 3395, 1805, 1625, 1465, 1165, 1025. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 5.07 s (1H,
H2), 4.43 m (1H, H3), 4.30 br.s (1H, OH), 3.27 m (1H,
H9), 3.23 m (1H, H7), 2.69 m (1H, H6), 2.31 br.s (1H,
H1), 1.97 d (1H, H8s), 1.70, 1.52 (12Hcycle), 1.50 d (1H,
2
H8an, J8s,8an- 11.1 Hz). Found, %: C 64.60; H 7.49;
3
H6, J6,7 4.6 Hz), 2.38 br.s (2H, H1), 1.92 d (2H, H8s),
1.47 d (2H, H8an, 2J8s,8an 10.7 Hz). Found, %: C 54.83;
H 6.19; N 5.83. C22H30N2O10. Calculated, %: C 54.77;
H 6.22; N 5.81.
N 4.99. C15H21NO4. Calculated, %: C 64.52; H 7.53;
N 5.02.
Compound XII was similarly obtained from 0.58 g
(2 mmol) of a mixture of compounds obtained by oxidation
of amide IIe, and 0.25 g (1.2 mmol) of dicyclohexyl-
carbodiimide. Yield 0.42 g (75%), mp 229–231°C, Rf 0.65
(C).
Azepanium exo-2-hydroxy-5-oxo-4-oxatri-
cyclo[4.2.1.03,7]-nonane-endo-9-carboxylate (XVI).
To 0.53 g (2 mmol) of compound IIe in 8 ml of glacial
acetic acid was added dropwise while stirring at room
temperature 0.23 ml (4 mmol) of 50% water solution of
hydrogen peroxide, and the stirring was continued at this
temperature for 10 days till the end of the reaction (TLC
monitoring). The acetic acid was removed in a vacuum,
to the oily residue was added ethyl ether, and after
endo-9-Morpholinocarbonyl-exo-2-hydroxy-4-
oxatricyclo[4.2.1.03,7]nonan-5-one (XXI). Yield
0.43 g (80%), mp 205–208°C, Rf 0.33 (Β). IR spectrum,
1
cm–1: 3420, 1795, 1630, 1460, 1130, 1080, 1015. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 5.10 br.s (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KAS’YAN et al.
1652
OH), 4.39 s (1H, H2), 4.31 d (1H, H3, 3J3,7 5.1 Hz), 3.73–
3.66, 3.59–3.44, 3.41–3.34 (8Hcycle), 3.29 d.d (1H, H9,
3J9,1 3.3, 3J6,9 9.4 Hz), 3.20 m (1H, H7), 2.74 d.d (1H, H6,
3J6,7 4.7 Hz), 2.33 br.s (1H, H1), 1.97 d (1H, H8s), 1.49 d
(1H, H8an, 2J8s,8an 10.2 Hz). Found, %: C 58.40; H 6.39;
N 5.25. C13H17NO5. Calculated, %: C 58.43; H 6.37;
N 5.24.
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