Lactonation of N-alkyl-and N,N-dialkylamido acids of norbornene series in reactions with performic acid

Article abstract of DOI:10.1134/S1070428007050053

Reaction products were obtained from bicyclo[2.2.1]hept-5-ene-endo,endo-2, 3-dicarboxylic (endic) acid anhydride and ammonia, methyl-, benzyl-, dimethyl-, methylbenzyl-, dibenzyl-, diethyl-, dipropyl-, diisopropyl-, and dipentylamines. The synthesized ami

Full text of DOI:10.1134/S1070428007050053

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 5, pp. 660−673. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.A. Pal’chikov, I.N. Tarabara, S.V. Shishkina, O.V. Shishkin, N.Yu. Kol’tsov, L.I. Kas’yan, 2007, published in Zhurnal Organicheskoi
Khimii, 2007, Vol. 43, No. 5, pp. 665−678.
Lactonation of N-Alkyl- and N,N-Dialkylamido Acids
of Norbornene Series in Reactions with Performic Acid
V. A. Pal’chikova, I. N. Tarabaraa, S. V. Shishkinab, O. V. Shishkinb,
N. Yu. Kol’tsovc, and L. I. Kas’yana
aDnepropetrovsk National University, Dnepropetrovsk, 49625 Ukraine
e-mail: cf@ff.dsu.dp.ua
bResearch and Technology Combine Institute of Single Crystals of Ukraine, Kharkov, Ukraine
cUkrainian State University of Chemical Technology, Dnepropetrovsk, Ukraine
Received April 6, 2006
Abstract—Reaction products were obtained from bicyclo[2.2.1]hept-5-ene-endo,endo-2,3-dicarboxylic (endic)
acid anhydride and ammonia, methyl-, benzyl-, dimethyl-, methylbenzyl-, dibenzyl-, diethyl-, dipropyl-, diiso-
propyl-, and dipentylamines. The synthesized amido acids were subjected to epoxidation by organic peracids.
The structure of compounds obtained was confirmed by IR, 1H and 13C NMR spectra, and in some instances , by
X-ray diffraction analysis.
DOI: 10.1134/S1070428007050053
the structure of the latter. The synthesis of amido acids
IIa–IIe completed within 1–2 days, the preparation of
compound IIf required 10 days (yield 40%). Amide IIf
was also synthesized by boiling initial reagents for 15 h
(yield 69%). The reactions of anhydride I with diethyl-,
dipropyl-, diisopropyl-, and dipentylamines continued up
to two weeks. We failed to prepare amido acids from
N-alkylanilines (N-methyl- and N-ethylaniline) both in
the cold and at boiling in benzene solution for 120 h
(TLC monitoring). It was established by 1H NMR spec-
troscopy that the only reaction product was bicyclo[2.2.1]-
hept-5-ene-endo,endo-2,3-dicarboxylic (endic) acid (III).
7
In contrast to numerous carboximides prepared with
the use of bicyclo-[2.2.1]hept-5-ene-endo,endo-2,3-
dicarboxylic acid anhydride (endic anhydride) (I), amido
acids based thereon are poorly understood [1–5]. The
N-alkylamides of bicyclo[2.2.1]hept-5-ene-endo,endo-
2,3-dicarboxylic acids were successfully used in repellent
compositions [6] and as agents possessing sedative action
[7]. The corresponding arylamides were applied in the
herbicide composition to cotton-plant protection [8], they
facilitate the germination of plant seeds [9]. The spectral
parameters of amido acids were not described. Known
amido acids were obtained by different procedures: by
heating reagents in alcohol [10], acetonitrile [11],
tetrahydrofuran [12], and dimethoxyethane [8].
1
2
6
NHR
2
O
O
In the present study we investigated reactions of endic
anhydride with ammonia and a series of monoalkyl- and
dialkylamines (methyl-, benzyl-, dimethyl-, methyl-
benzyl-, dibenzyl-, diethyl-, dipropyl-, diisopropyl-, and
dipentylamines).
3
C H
6
6
4
5
COOH
C
O
NR
2
O
_
I
IIа к
NR2 = NH2 (a), NHCH3 (b), NHCH2Ph (c), N(CH3)2 (d),
N(CH3)CH2Ph (e), N(CH2Ph)2 (f), N(C2H5)2 (g),
N(C3H7)2 (h), N(iso-C3H7)2 (i), N(C5H11)2 (j).
Amido acids IIa–IId were described before [7, 13–
16], the other compounds we obtained for the first time.
Amido acids IIa–IIj were prepared by reaction of
equimolar quantities of reagents in benzene solution at
room temperature (TLC monitoring). The time of the
reaction between anhydride I and amines depended on
IR spectra of compounds IIa–IIc contained absorp-
tion bands in the regions 1670–1650 (CO), 1267–1252
(CN), and 3362–3280 cm–1 (NH), and also in the range
660

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
661
1770–1700 cm–1 characteristic of the carboxy group. In
the spectra of amides IId–IIj the carbonyl group vibra-
tions gave rise to bands at 1685–1625 and 1758–
1690 cm–1.Absorption bands belonging to the unsaturat-
ed fragments of amides IIa–IIj appeared in the regions
3068–3010 and 745–700 cm–1 corresponding to the
stretching and bending vibrations of the =C–H bonds
[17]. The bands of stretching vibrations of the strained
double bond (1575–1550 cm–1) are weak, and in the
spectra of secondary amides IIb and IIc and of primary
amide IIa they are overlapped by the band of the NH
bond [18].
anhydride epoxy derivative VI [22]. The reactions
proceeded under mild conditions in weakly alkaline
medium originating from the presence of the amines.
7
4
HO
5
3
RCO3H
2
6
1
C
O
C
O
NHR
O
IV
1
HO
The structure of amido acids was confirmed by H
O
and 13C NMR spectra. 1H NMR spectra of amido acids
contained all necessary signals: resonances of olefin
protons H5 and H6 in the region 5.93–6.32 ppm, of
bridgehead protons H1 and H4 in the range 2.86–3.05
ppm, and of protons H2, H3 at the carbonyl groups of
the amido acids at 2.96–3.38 ppm. The latter protons in
the spectra of compounds IIb–IId are essentially
nonequivalent; their coupling corresponds to vicinal con-
stants 10.2, 10.0, and 10.1 Hz unambiguously confirming
the exo-orientation of these protons on the framework
fragment. The signals of bridging protons H7s and H7an
are closely located (1.11–1.35 ppm) and coupled with
the constant 8.0–9.1 Hz.
O
C(O)NHR
O
O
C
O
O
V
VI
We chose for oxidation of amido acids the performic
acid that was prepared in situ from 98% formic acid and
50% water solution of hydrogen peroxide. The oxidation
of amido acids IIa, IIb, IId–IIf, and IIh–IIj was carried
out using double molar excess of the oxidant at 0°C (TLC
monitoring). The successful application of the performic
acid was underpinned by its high acidity and reactivity
as an electrophilic oxidative reagent with respect to
In the 13C NMR spectra of amido acids IIa and IIb,
like in the 1H NMR spectra, the signals of atoms C5 and
C6, C1 and C4, C2 and C3, and also of the carbon atoms
of the carbonyl groups did not coincide (Fig. 1).
7
1
2
6
Amido acids possess several reactive sites (strained
double bond, carboxy and carboxamide groups), they are
capable to be converted into other class compounds
involving these sites.
3
5
4
COOH
O
NHCH3
Unlike imides of norbornene series whose reactions
with organic peracids were often described [5, 19], the
oxidation of amido acids was hardly studied before. The
only example concerns the oxidation of an amido acid
containing a phenylethyl group where the products have
not been identified [2].
C
C=O
The oxidation of amido acids can lead both to epoxy
derivatives and to products of their heterocyclization
involving the carboxy and amide groups. Such hetero-
cyclizations of substituted norbornenes are known, in
particular, lactone IV was obtained by epoxidation of
various bicyclo-[2.2.1]hept-5-ene-2-carboxamides with
the endo-orientation of the substituent in the presence of
a large excess (4:1) of peracids [20, 21].
CH3
20
C
C
C
C
180 160 140 120 100 80
, ppm
60
40
Fig. 1. 13C NMR spectrum of endo-3-(N-methylcarbamoyl)-
bicyclo-[2.2.1]hept-5-ene-endo-2-carboxylic acid (IIb)
(DMSO-d6, 100.57 MHz).
The formation of amidolactones V was observed in
reactions with amines (RNH2, R = H, Ph, CH2Ph) of endic
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

PAL’CHIKOV et al.
662
substrates of considerably reduced nucleophilicity of the
olefin due to the presence of two electron-withdrawing
substituents [23].
products obtained from amides IIb and IId were
identical.
The structure of one among the typical oxidation
products, salt XVI obtained by oxidation of amide IIj
with performic acid, was proved by X-ray diffraction
study (Fig. 2). The independent part of the unit cell
contains two molecules of lactonoacid X (A and Β)
and two molecules of amine (C and D). The leveling of
bond lengths O4–C8 and O5–C8 in molecules A and Β
{O4–C8 1.212(3) (A and Β), O5–C8 1.224(3) (A) and
We showed formerly [24] that oxidation of amido
acids VII of the norbornene series with fragments of
nonaromatic heterocyclic amines resulted in most cases
in two types of substances: amidolactones VIII and salts
IX of lactonoacid X with the amines contained in amide
groups composition (Scheme 1).
The oxidation of amido acids IIa–IIj also led to the
formation of two types of compounds: lactonoacid X and
salts XI–XVI of lactonoacid X with the corresponding
amines (Scheme 2).
°
1.252(3) A (Β) comparable with an average bond length
[26] 1.250 A in carboxylate anion}, and also the
objectively revealed positions of hydrogen atoms at
nitrogens in molecules C and D permit a conclusion that
molecules A and Β are anions which form salts with
cations of dipentylammonium (C and D).
Acid X was previously described in [15, 20, 25]; in
this study it was also prepared by known methods: It
was isolated from oxidation products of endic acid (III)
and anhydride I. The melting point, TLC data, and
spectral behavior of compound X and the oxidation
The five-membered heterocycle is in an envelop
conformation. The deviation of C6 atom from the mean-
Scheme 1.
HO
HO
2 equiv HCO3H, 0оС
_
+
HCOOH
CONR2
COOH2NR2
COOH
NR2
O
C
O
C
C
O
O
O
VII
VIII
IX
NR2 = cycloalkyl.
Scheme 2.
8
2 equiv HCO3H,
0oС
HCOOH
2 equiv HCO3H,
HO
1
2
9
0oС
6
3
7
COOH
COOH
HCOOH
COOH
O4
5
C
C
C
O
NHCH3
O
N(CH3)2
O
IId
IIb
X
8
HO
2 equiv HCO3H,
1
2
9
0oС
_
COO H2+NR2
6
3
7
HCOOH
COOH
4
O
5
C
C
O
NR2
O
IIа, IIe, IIf, IIh_j
XI_XVI
NR2 = NH2 (XI), N(CH3)CH2Ph (XII), N(CH2Ph)2 (XIII), N(C3H7)2 (XIV), N(iso-C3H7)2 (XV), N(C5H11)2 (XVI).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
663
°
square plane of the other atoms of the ring is –0.60 A in
C
°
molecule A and 0.66 Ain molecule Β. The hydroxy group
C
C
C
at C2 atom of the bicycloheptane fragment has an exo-
orientation, and the substituent at C4 atom, endo-
orientation [torsion angles O3C2C3C4 in molecules A and
Β are –179.5(2) and –178.6(2)° respectively, C2C3C4C8
in molecules A and Β are 66.5(3) and 63.0(3)°
O
C
C
O
C
C
C
O
O
respectively]. This position of substituents results in a
C
N
C
C
°
C
...
shortened intramolecular contact H2 C8 2.77 A in
°
C
C
molecule A and 2.59 A in molecule Β (the sum of van
C
C
C
°
der Waals radii is 2.87A[27]).
In the crystal the anions and cations are bound by
Fig. 2. Molecular structure of dipentylammonium exo-2-
hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-endo-9-
carboxylate (XVI) according to X-ray diffraction analysis
...
...
intermolecular hydrogen bonds O3a–H3aa O5’b (H
O
°
°
...
...
...
1.86 A, O–H O 174°), O3b–H3ba O4’a (H O 1.89 A,
...
...
...
O–H O 176°), N1a–H1Na O5’a (1 – x, –y, –z) (H
O
°
...
...
1.96 A , N–H O 164°), N1a–H1Nb O5a (x, 1 + y, z)
yield of target product XVII. The replacement of the
formic acid solvent by a mixture of dichloromethane and
acetonitrile somewhat decreased the yield, and the use
of peracetic acid instead of performic acid decelerated
the oxidation and required more rigid reaction conditions.
°
...
...
...
(H O 1.91 A, N–H O 155°), N1b–H1Nc O5’b (–x, –y,
°
...
...
...
1 – z) (H O 1.83 A, N–H O 169°), N1b–H1Nd O4b
°
...
...
(H O 1.85 A, N–H O 160°).
By an example of amido acid IIc we studied the effect
of the peracid character and the oxidation conditions on
the yield of the reaction product, benzylammonium exo-
2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-endo-
9-carboxylate (XVII) (Scheme 3).
The oxidation of diethylamide IIg with peracetic acid
prepared in situ yielded salt XVIII of lactonoacid X
(Scheme 4). The peracetic acid was obtained in two ways:
by reaction of glacial acetic acid with 50% water solution
of hydrogen peroxide, and by reaction of acetic anhydride
with hydrogen peroxide in chloroform in the presence
The data obtained showed an important fact: The
increased amount of performic acid did not affect the
Scheme 3.
2 equiv HCO3H, HCOOH
0оC, 3 days, 75.0%
4 equiv HCO3H, HCOOH
HO
0оC, 3 days, 74.0%
2 equiv HCO3H,
_
+
COO H3NCH2Ph
COOH
CH2Cl2:CH3CN, 3:1
0оC, 13 days, 70.5%
C
O
C
O
O
NHCH2Ph
IIc
XVII
2 equiv CH3CO3H, CH3COOH
17оC, 5 days, 69.5%
Scheme 4.
HO
2 equiv CH3CO3H
_
+
H2N(C2H5)2
COO
COOH
O
C
C
O
N(C2H5)2
O
IIg
XVIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

PAL’CHIKOV et al.
664
of sodium bicarbonate; the yield of oxidation product
was 63 and 65% respectively.
diffraction study on a single crystal of the compound
(Figs. 3 and 4). The independent part of the unit cell of
the crystal contains two molecules (E and F) and a
diethylammonium cation. The bond lengths O4a–C9a
The treatment of compound IIg with 54% m-chloro-
perbenzoic acid in dichloromethane and with freshly
prepared crystalline 65% monoperoxyphthalic acid in
ethyl acetate provided salt XVIII in 31 and 49% yield
respectively. In all four cases the oxidation was carried
out at room temperature using two equiv of the oxidant;
the reaction time was 5, 4, 2, and 2 days respectively
(TLC data).
°
1.184(6), O5a–C9a 1.300(6), and C6a–C9a 1.480(7) A in
molecule E are comparable with the average bond lengths
°
(1.210, 1.308, and 1.502 A respectively) of a neutral
carboxy group [26]. In molecule F the bond lengths O4c–
°
C9c 1.223(6) and O5c–C9c 1.257(6) A are closer to each
°
other, the bond C6c–C9c [1.508(7) A] is longer than in
molecule Ε, and they are comparable with the bond
These results were quite different from those obtained
by oxidation of amide IIg with performic acid in situ in
the presence of a double molar amount of the oxidant at
0°C. Under these conditions an equimolar mixture
formed of lactonoacid X and its salt with diethylamine
XVIII as demonstrated by 1H NMR spectrum.
lengths in a carboxylate anion (O4–C9 and O5–C9 1.254,
°
C6–C9 1.520 A ). The above findings suggest that
molecule Ε exists in the crystal in a neutral form, and
molecule F is a carboxylate anion forming a salt with
the diethylammonium cation.
The five-membered heterocycle is in an envelop
conformation. The deviation of C2 atom from the mean-
°
square plane of the other atoms of the ring is –0.62 A in
molecule E and 0.66Ain molecule F. The hydroxy group
at C4 atom of the bicycloheptane fragment has an exo-
orientation, and the substituent at C6 atom, endo-
orientation [torsion angles C2C3C4O3 in molecules E
and F 107.3(4) and 108.7(5)° respectively; C2C1C6C9
in molecules E and F 134.2(4) and 136.5(4)°
respectively]. This orientation of the carboxy group
...
results in a shortened intramolecular contact H4aa C9a
°
°
2.65 A in molecule E and 2.70 A in molecule F (the sum
°
of van der Waals radii is 2.87 A [27]). Therewith the
carboxy group is turned with respect to the C1–C6 bond
[torsion angle C1C6C9O4 in molecules E and F –21.6(8)
and –35.1(6)° respectively].
The structure of the oxidation product obtained from
amido acid IIg was finally established by X-ray
In the crystal of the oxidation product of amido acid
IIg molecule Ε, anion F, and diethylammonium cation
are bound by intermolecular hydrogen bonds O3c–
Fig. 3. Molecular structure of oxidation product obtained from
amido acid IIg according to X-ray diffraction analysis.
Fig. 4. Molecular structure of lactonoacid X according to X-
ray diffraction analysis.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
665
°
...
...
orientation of substituents attached to atoms C6 and C9
is revealed by the values of the vicinal coupling constants
of the protons linked to this carbon atoms (10.5–
10.8 Hz). The signals of the exo-protons at C6 and C9
atoms (doublets in the regions 2.48–2.64 and 2.82–
3.52 ppm respectively) suffer additional splitting by the
coupling with protons H1 and H7. It is worth mentioning
that the chemical shifts of the bridgehead protons (H1,
H7) are different since the latter is additionally included
into the five-membered lactone. A crucial evidence is
the presence of a signal in the region 7.35–8.47 ppm
belonging to the resonance of equivalent protons attached
to the ammonium nitrogen. The integral intensity of the
latter signal in the 1H NMR spectrum registered in CDCl3
for the oxidation product obtained by treating amide IIg
with performic acid definitely indicates equimolar ratio
of the reaction products, lactonoacid X and salt XVIII.
The amount of hydrogen atoms of ethyl groups in the
cation part of compound XVIII and methylene groups
in compound XVIII are strictly equivalent thus addi-
tionally confirming the suggested salt-like structure. The
1H NMR spectrum of acid X in respect to the reciprocal
position of signals from the framework is like the
1H NMR spectra of salts XI–XVIII. A distinguishing
feature of the acid X spectrum is only the lack of the
signals from protons at the ammonium nitrogen and from
the alkyl groups.
H3cc O5c' (0.5 + x, 0.5 – y, 0.5 + z) (H O 1.86 A,
...
...
O–H O 172°), O3a–H3ac
O
4c' (0.5 + x, 0.5 – y, 0.5 + z)
°
...
...
...
(H O 1.81 A, O–H O 172°), N1b–H1be
O
4a' (0.5 + x,
°
...
...
0.5 – y, 0.5 + z) (H O 1.90 A, N–H O 163°), N1c–
°
...
...
H1bd
O
5c' (0.5 + x, 0.5 – y, 0.5 + z) (H O 1.80 A,
...
...
N–H O 173°), O5a–H5ac O3a (–0.5 + x, 0.5 – y, –0.5 +
°
...
...
z) (H O 1.82 A, O–H O 171°).
The structure of the other compounds was studied by
IR and 1H NMR spectroscopy.
In the IR spectra of products obtained by oxidation
of amido acids IIa, IIc, IIe–IIj and isolated as salts XI–
XVIII the stretching vibrations of the hydroxy and
ammonium groups were observed as broad bands in the
regions 3415–3212 and 2650–2495 cm–1 (“ammonium
band”); the latter in the spectra of salts XI and XVII
appeared in characteristic regions 3060 and 3014 cm–1
respectively. A characteristic feature of the IR spectra of
all the salts in question is the narrow range of frequencies
(1790–1766 cm–1) corresponding to the absorption of
the carbonyl from the γ-lactone ring. The bands in the
region 1604–1585 and 1368–1350 cm–1 were assigned
to antisymmetric and symmetric vibrations of the
carboxylate anion. The scissor bending vibrations of the
latter appeared as a weak peak in the region 790–
763 cm–1 [28]. The fragment C−O–C of the five-
membered lactone ring gave rise to an absorption band
in the range 1030–1014 cm–1 [18].
The decomposition under the electron impact of the
product of amide IIg oxidation, salt XVIII, confirms the
presence in the molecule of a lactone ring. The diethyl-
ammonium cation eliminates a proton under the electron
impact transforming into diethylamine (m/z 73). Further
the proton evidently is captured by the anion of exo-2-
hydroxy-5-oxo-4-oxatricyclo-[4.2.1.03,7]nonane-endo-9-
carboxylic acid contained in the composition of salt
XVIII giving compound X whose decomposition during
measuring the mass spectrum is shown in the scheme.
The analysis of lactonoacid X decomposition revealed
the following fragmentation routes: path a where the
primary decomposition of the molecular ion occurred
with a loss of carbon dioxide molecule, of a carbon
monoxide, and water to form cation-radical Φ1 (m/z 108)
undergoing a series of unstable transformation to give
finally cyclopentadienyl cation Φ2 (m/z 65); path b with
a loss of a carbon monoxide molecule from the molecular
ion providing ion Φ3 (m/z 126) that decomposed by two
routes. On the one hand elimination of water and carbon
monoxide resulted in formation of ions Φ4 (m/z 108)
and Φ5 (m/z 80), on the other hand, a loss of a formyl
1
In the complex H NMR spectra of salts XI–XVIII
the key signals of protons H2 and H3 deshielded due to
the neighbor oxygen-containing substituents appeared in
the region 4.03–4.26 and 4.22–4.45 ppm. The first signals
is a singlet, the second is a doublet because of the
coupling with proton H7 (3J3,7 4.8–5.6 Hz). The endo-
H
+
RCO3H
O
IIа, IIc, IIe_j
COOH
NR2
C
O
XIX
HO
HO
_
H2O
+
COO
H2NR2
COOH
O
C
O
C
O
+
NR2
XI_XVIII
XX
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PAL’CHIKOV et al.
666
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LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
667
20% hydrochloric acid. We succeeded in separating the
reaction products owing to different solubility of acid X
and benzylamine hydrochloride in hot acetone.
radical yielded ion Φ6 (m/z 97) that suffered a series of
transformation on the way to dehydrofuran cation-radical
Φ7 (m/z 70). The processes of ions Φ3, Φ4, Φ5, Φ6, and
Φ7 formation are confirmed by the corresponding
metastable transitions. The routes of other ions formation
are indicated in the Scheme 5.
By an example of lactonoacid X and diethylamine
we showed the possibility to obtain and isolate in a free
state salt XVIII, and also the ready formation of the
corresponding amidolactone XXI (Scheme 6). The yield
of the latter was considerably higher (by 18%) in its
preparation from salt XVIII as compared with the
synthesis by successive treatment of compound X with
diethylamine and a dichloromethane solution of dicyclo-
hexylcarbodiimide (DCC) in the cold.
The data obtained suggested an approach to
understanding the formation of salt-like products under
the oxidation conditions. Salts XI–XVIII were obtained
as a result of a nucleophilic attack by the oxygen of
carboxamide group on the contiguous electrophilic
carbon of the protonated epoxide XIX followed by
hydrolysis of iminium intermediate XX and accompanied
by transfer of a proton from the carboxy group to the
amine molecule formed in hydrolysis.
Analogously salt XVI was converted into the cor-
responding amidolactone XXII (Scheme 7). Inasmuch
as bulky substituents at the nitrogen atom in this case
considerably hampered the synthesis compared to the
preparation of amidolactone XXI compound XXII was
obtained under more stringent conditions and during
longer time.
Salt XVII was converted into lactonoacid X by treat-
ing the water solution of the former with an equmolar
HO
HCl
The IR spectrum of compound XXI contained
absorption bands of two carbonyls: lactone (1800 cm–1)
and amide (1620 cm–1) ones. The stretching vibrations
of the hydroxy group give rise to a broad band in the
region 3420 cm–1. The spectrum contained also a strong
+ PhCH2NH2 HCl
XVII
COOH
H2O
O
C
O
X, 51%
Scheme 6.
HO
HO
HN(C2H5)2
_
+
COOH
COO H2N(C2H5)2
CH2Cl2 or (CH3)2CO, 0оC, 98%
O
C
O
C
O
O
X
XVIII
DCC, CH2Cl2,
0oC, 4 days,
96.3%
HO
(1) HN(C2H5)2
(2) DCC
CH2Cl2, 0оC, 4 days, 78.4%
C(O)N(C2H5)2
O
C
O
XXI
Scheme 7.
HO
HO
DCC, 20oC
CH2Cl2, 3 weeks, 53%
_
+
COO H2N(C5H11)2
C(O)N(C5H11)2
O
C
O
C
O
O
XXII
XVI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

PAL’CHIKOV et al.
668
°
β 68.57(1), γ 72.54(2)°, V 2064.3(6) A3, Mr 709.92, Z 2,
space group P1, dcalc 1.142 g/cm3, μ(MoKα) 0.082 mm–1,
F(000) 774. Unit cell parameters and intensities of 18665
reflections (7268 independent reflections, Rint 0.025)
were measured on a diffractometer Xcalibur-3 (MoKα
radiation, CCD-detector, graphite monochromator,
ω-scanning, 2θmax 50°).
narrow peak in the region 1030 cm–1 assigned to the
vibrations of the fragment C–O–C involved into the five-
membered lactone ring [18].
The 1H NMR spectra of compounds XXI and XXII
contain all expected signals: endo-Proton H2 and exo-
proton H3 give rise to peaks in the region 4.41–4.43 and
4.29 ppm respectively, a complex multiplet of H7 proton
is located at 3.17–3.19 ppm, the signals from the bridging
protons H8s and H8an (1.96 and 1.52–1.53 ppm) suffer
splitting due to the coupling with a geminal constant
10.4–10.5 Hz. Doublets of H6 and H9 protons appear at
2.65–2.68 and 3.02–3.15 ppm respectively and are
additionally split by coupling with H1 and H7 protons;
The structure was solved by the direct method using
SHELXTL software [29]. The hydrogen atoms positions
are calculated from geometric considerations, and those
of hydrogen atoms at the nitrogen in cations C and D
were revealed from the difference synthesis of the
electron density. All hydrogen atoms positions were
refined in the rider model with Uiso = nUeq (n = 1.5 for
methyl and hydroxy groups and n = 1.2 for the other
hydrogen atoms). The structure was refined by F2 in full-
matrix least-mean-square anisotropic approximation for
nonhydrogen atoms till wR2 0.225 for 7089 reflections
(R1 0.069 for 3433 reflections with F > 4σ(F), S 0.923).
The crystallographic data, atomic coordinates, and
geometrical parameters of the structure are deposited in
the Cambridge Structural Database (structure no. CCDC
299796).
3
the value of the vicinal constant J6,9 10.2 Hz
unambiguously con-firms their exo-orientation. A char-
acteristic feature of the 1H NMR spectrum of compound
XXI is a pronounced nonequivalence of the protons of
the ethyl groups in the carboxamide moiety: They appear
as two two-proton quartets (3.12 and 3.32 ppm) and two
three-proton triplets (0.96 and 1.13 ppm). In the 1H NMR
spectrum of com-pound XXII the nonequivalence of
pentyl group protons is considerably less pronounced (Δδ
0.03 ppm) only for the methylene groups attached directly
to the nitrogen of the amide.
The oxidation product of amide IIg, mixed crystals
of lactonoacid X (50%) and salt XVIII (50%) mono-
clinic, C9H10O5, C9H9O5C4H12N , at –109°C a 13.172(3),
b 19.679(4), c 10.123(2) A, β 122.46(1)°, V 2214.1(8) A3,
Mr 469.48, Z 4, space group Cc, dcalc 1.408 g/cm3,
μ(MoKα) 0.111 mm–1, F(000) 1000. Unit cell parameters
and intensities of 2038 independent reflections were
measured on an automatic four-circle diffractometer
Siemens P3/PC (MoKα, , θ/2θ scanning, 2θmax 50°).
The sum of data (the lack of the ammonium band in
the IR spectra and of signals in the region 7.0–8.5 ppm
of the 1H NMR spectra, nonequivalence of 1H nuclei in
alkyl fragments) confirms that the structures of amido-
lactones assigned to compounds XXI and XXII are valid.
–
+
·
°
°
EXPERIMENTAL
IR spectra were recorded on spectrometers UR-20 and
Paragon 500 FT-IR (Perkin Elmer) from samples
pelletized with potassium bromide. 1H NMR spectra were
registered on spectrometers Varian VXR at operating
frequencies 200 and 300 MHz from solutions in
deuterdimethyl sulfoxide and deuterochloroform, internal
reference TMS. 13C NMR spectra were registered on
a spectrometer Gemini-400BB at operating frequency
100.57 MHz. Mass spectrum of salt XVIII was measured
on Varian 1200L instrument at ionizing electrons energy
70 eV. The reaction progress was monitored and the
purity of compounds synthesized was checked by TLC
on Silufol UV-254 plates, eluents ethyl ether (A) and
2-propanol (B), development in iodine vapor. Elemental
analysis was performed on Carlo Erba analyzer.
The structure was solved by the direct method using
SHELXTL software [29]. The hydrogen atoms positions
are calculated from geometric considerations for the
bicycloheptane framework and revealed from the
difference synthesis of the electron density for the
substituents at the framework fragment and for
diethylammonium cation. All hydrogen atoms positions
were refined in the rider model with Uiso = nUeq (n = 1.5
for methyl and hydroxy groups and n = 1.2 for the other
hydrogen atoms). The structure was refined by F2 in full-
matrix least-mean-square anisotropic approximation for
nonhydrogen atoms till wR2 0.103 for 1973 reflections
(R1 0.044 for 1446 reflections with C F > 4σ(F), S 1.058).
The crystallographic data, atomic coordinates, and
geometrical parameters of the structure are deposited in
the Cambridge Structural Database (structure no. CCDC
299802).
Crystals of salt XVI triclinic, C9H9O5–×C10H24N+, at
°
20°C a 11.946(2), b 13.814(3), c 14.197(2)A, α 77.30(1),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
669
2.96 m (1H, H4), 1.35 d (1H, H7s), 1.20 d (1H, H7an
,
Reaction of bicyclo[2.2.1]-hept-5-ene-endo,endo-
2J7s,7an 8.5 Hz).
2,3-dicarboxylic acid anhydride (I) with monoalkyl-
and dialkylamines. To 3.28 g (0.02 mol) of endic
anhydride (I) in 20–25 ml of anhydrous benzene was
added at stirring 0.02 mol of an appropriate amine
(ammonia and methylamine were used as 25% water
solutions, dimethylamine, as 0.5 M benzene solution).
The reaction mixture was stirred at room temperature
till completion of the reaction (from 1 day to 3 weeks,
TLC monitoring), the separated crystals were filtered off,
washed on the filter with benzene, and dried in air. The
products were additionally purified by recrystallization
from benzene or 2-propanol. This procedure was applied
to the synthesis of amido acids IIa–IIj.
endo-3-(N,N-Dimethylcarbamoyl)bicyclo-[2.2.1]-
hept-5-ene-endo-2-carboxylic acid (IId). Yield 3.09 g
(74%), mp 150–151°C [15], Rf 0.83 (A). IR spectrum,
cm–1: 3455, 3020, 1750, 1645, 1530, 1340, 1200, 718.
1H NMR spectrum (300 MHz, DMSO-d6), δ, ppm:
11.74 s (1H, COOH), 6.22 d.d (1H, H6), 5.93 d.d (1H,
3
3
H5, 3J5,6 5.3, J4,5 = J6,1 = 2.8 Hz), 3.38 d.d (1H, H2),
3.29 d.d (1H, H3, 3J2,3 10.1, 3J1,2 = 3J3,4 = 3.0 Hz), 3.03 m
(1H, H1), 2.92 m (1H, H4), 2.92 C (3H, CH3), 2.69 s (3H,
CH3), 1.34 d (1H, H7s), 1.22 d (1H, H7an, 2J7s,7an 8.1 Hz).
endo-3-(N-Methyl-N-benzylcarbamoyl)bicyclo-
[2.2.1]hept-5-ene-endo-2-carboxylic acid (IIe). Yield
4.85 g (85%), mp 135.5–136°C, Rf 0.61 (A), 0.67 (B).
IR spectrum, cm–1: 3460, 3010, 1750, 1625, 1505, 1460,
1425, 1345, 1265, 1195, 705. Found, %: C 71.51; H 6.71;
N 4.99. C17H19NO3. Calculated, %: C 71.58; H 6.67;
N 4.91.
endo-3-Carbamoylbicyclo[2.2.1]hept-5-ene-endo-
2-carboxylic acid (IIa). Yield 3.26 g (90%), mp 137–
138°C [14]). Rf start (A), 0.80 (B). IR spectrum, cm–1:
3450, 3362, 3080, 3050, 1700, 1670, 1540, 1395, 1338,
1
1252, 1200, 790, 700. H NMR spectrum (200 MHz,
DMSO-d6), d, ppm: 7.27 s (1H, NH), 6.58 s (1H, NH),
endo-3-(N,N-Dibenzylcarbamoyl)bicyclo-[2.2.1]-
hept-5-ene-endo-2-carboxylic acid (IIf). Yield 2.89 g
(40%), mp 139.5–140°C, Rf 0.13 (A), 0.76 (B). IR
spectrum, cm–1: 3420, 3010, 1710, 1625, 1540, 1495,
1255, 712. 1H NMR spectrum (200 MHz, DMSO-d6), δ,
ppm: 7.42–7.29 (10Harom), 6.09 m (2H, H5, H6), 3.85 s
(4H, 2CH2), 3.09 m (2H, H2, H3), 3.05 m (2H, H1, H4),
1.28 d (1H, H7s), 1.20 d (1H, H7an, 2J7s,7an 8.2 Hz). Found,
%: C 76.49; H 6.41; N 3.86. C23H23NO3. Calculated, %:
C 76.45; H 6.37; N 3.88.
6.17 d.d (1H, H6), 5.94 d.d (1H, H5,3J5,6 5.1, 3J4,5 = 3J6,1
=
3.1 Hz), 3.16 d.d (1H, H2), 3.14 d.d (1H, H3), 3.05 m
(1H, H1), 3.02 m (1H, H4), 1.20 d (1H, H7s), 1.12 d
(1H, H7an, 2J7s,7an 8.2 Hz). 13C NMR spectrum (DMSO-
d6), d, ppm: 174.6 (C=O), 173.9 (C=O), 136.0 (C6), 134.0
(C5), 49.3 (C2), 48.9 (C3), 48.8 (C7), 47.6 (C1), 47.2 (C4).
endo-3-(N-Methylcarbamoyl)bicyclo[2.2.1]-hept-
5-ene-endo-2-carboxylic acid (IIb).Yield 3.51 g (90%),
mp 155–157°C (155°C [7]), Rf 0.06 (A), 0.73 (B). IR
spectrum, cm–1: 3326, 3050, 1750, 1650, 1550, 1425,
1260, 714. 1H NMR spectrum (300 MHz, DMSO-d6), δ,
ppm: 7.64 br.s (1H, NH), 6.16 d.d (1H, H6), 5.94 d.d
(1H, H5, 3J5,6 5.5, 3J4,5 = 3J6,1 = 3.1 Hz), 3.13 d.d (1H,
H2), 3.06 d.d (1H, H3, 3J2,3 10.2, 3J1,2 = 3J3,4 = 3.1 Hz),
3.01 m (1H, H1), 2.92 m (1H, H4), 2.48 s (3H, CH3),
endo-3-(N,N-Diethylcarbamoyl)bicyclo[2.2.1]-
hept-5-ene-endo-2-carboxylic acid (IIg). Yield 4.08 g
(86%), mp 102–104°C, Rf 0.31 (A), 0.72 (B). IR
spectrum, cm–1: 3460, 3010, 1745, 1625, 1480, 1405,
1280, 1190, 730. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 11.60 s (1H, COOH), 6.16 d.d (1H, H6),
5.98 d.d (1H, H5, 3J5,6 5.3, 3J4,5 = 3J6,1 = 2.7 Hz), 3.38 q
(2H, CH2), 3.11 q (2H, CH2), 3.01 d.d (1H, H2), 2.96 d.d
(1H, H3), 2.90 m (1H, H1), 2.86 m (1H, H4), 1.34 d (1H,
H7s), 1.20 d (1H, H7an, 2J7s,7an 8.1 Hz), 1.10 t (3H, CH3),
0.92 t (3H, CH3). Found, %: C 65.89; H 7.99; N 5.79.
C13H19NO3. Calculated, %: C 65.82; H 8.02; N 5.91.
2
1.26 d (1H, H7s), 1.20 d (1H, H7an, J7s,7an 8.0 Hz).
13C NMR spectrum (DMSO-d6), δ, ppm: 173.4 (C=O),
171.5 (C=O), 134.8 (C6), 133.7 (C5), 48.3 (C2), 48.2 (C3),
48.1 (C7), 46.6 (C1), 45.3 (C4), 25.5 (CH3).
endo-3-(N-Benzylcarbamoyl)bicyclo[2.2.1]-hept-5-
ene-endo-2-carboxylic acid (IIc). Yield 4.88 g (90%),
mp 118–119.5°C (118–120°C [15]), Rf 0.49 (A), 0.78
(B). IR spectrum, cm–1: 3280, 3030, 1770, 1650, 1514,
endo-3-(N,N-Dipropylcarbamoyl)bicyclo-[2.2.1]-
hept-5-ene-endo-2-carboxylic acid (IIh). Yield 4.29 g
(81%), mp 111–112.5°C, Rf start (A), 0.57 (B). IR
spectrum, cm–1: 3450, 3010, 1742, 1582, 1482, 1420,
1
1486, 1267, 1207, 745. H NMR spectrum (200 MHz,
DMSO-d6), δ, ppm: 7.26 m (5Harom), 6.69 br.s (1H, NH),
6.32 d.d (1H, H6), 5.98 d.d (1H, H5, 3J5,6 5.2, 3J4,5 = 3J6,1
1
2
1350, 1312, 735, 710. H NMR spectrum (300 MHz,
= 3.0 Hz), 4.26 d (1H, NCH), 4.06 d (1H, NCH, JH,H
14.3, 2JHNH 5.5 Hz), 3.16 d.d (1H, H2), 3.11 d.d (1H, H3,
DMSO-d6), δ, ppm: 6.05 m (2H, H5, H6), 3.15 m (2H,
3
3
3J2,3 10.0, J1,2 = J3,4 = 3.0 Hz), 3.01 m (1H, H1),
H2, H3), 3.00 m (2H, H1, H4), 2.70 t (4H, 2CH2), 1.58 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

PAL’CHIKOV et al.
670
(4H, 2CH2), 1.25 m (2H, H7s, H7an), 0.95 t (6H, 2CH3).
Found, %: C 67.98; H 8.60; N 5.36. C15H23NO3.
Calculated, %: C 67.92; H 8.68; N 5.28.
acid was removed in a vacuum, ethyl ether was added to
the oily residue, and after prolong at grinding in the cold
the formed crystals were filtered off and dried. This
procedure was used in preparation of compounds XI–
XVIII.
endo-3-(N,N-Diisopropylcarbamoyl)bicyclo-
[2.2.1]hept-5-ene-endo-2-carboxylic acid (IIi). Yield
2.12 g (40%), mp 137–138.5°C, Rf 0.19 (B). IR spectrum,
cm–1: 3460, 3050, 1690, 1625, 1600, 1490, 1400, 1340, 1220,
1165, 740, 725. Found, %: C 67.86; H 8.75; N 5.25.
C15H23NO3. Calculated, %: C 67.92; H 8.68; N 5.28.
Ammonium exo-2-hydroxy-5-oxo-4-oxatricyclo-
[4.2.1.03,7]nonane-endo-9-carboxylate (XI). Yield
0.37 g (86%), mp 155–158°C, Rf 0.06 (B). IR spectrum,
cm–1: 3215, 3060, 1780, 1725, 1595, 1425, 1360, 1175,
1025, 790. 1H NMR spectrum (200 MHz, DMSO-d6), δ,
ppm: 8.36 br.s (4H, H4N+), 6.19 br.s (1H, OH), 4.26 d
(1H, H3, 3J3,7 5.6 Hz), 4.06 s (1H, H2), 3.13 m (1H, H7),
2.90 d.d (1H, H9, 3J9,1 3.7, 3J6,9 10.5 Hz), 2.54 d.d (1H,
endo-3-(N,N-Dipentylcarbamoyl)bicyclo-
[2.2.1]hept-5-ene-endo-2-carboxylic acid (IIj). Yield
4.56 g (71%), mp 135–137°C, Rf Ctapt (A), 0.63 (B). IR
spectrum, cm–1: 3126, 3068, 1728, 1564, 1464, 1422,
3
H6, J6,7 5.0 Hz), 2.36 br.s (1H, H1), 1.90 d (1H, H8s),
1
1378, 1288, 1202, 720. H NMR spectrum (200 MHz,
1.44 d (1H, H8an, 2J8s,8an 10.5 Hz). Found, %: C 50.30;
H 6.02; N 6.59. C9H13NO5. Calculated, %: C 50.23;
H 6.05; N 6.51.
DMSO-d6), δ, ppm: 6.04 m (2H, H6, H5), 3.09 m (2H,
H2, H3), 2.95 m (2H, H1, H4), 2.81 t (4H, 2CH2), 1.52 m
(4H, 2CH2), 1.27 m (8H, 4CH2), 1.21 d (1H, H7s), 1.11 d
(1H, H7an, 2J7s,7an 9.1 Hz), 0.85 t (6H, 2CH3). Found, %:
C 70.99; H 9.71; N 4.28. C19H31NO3. Calculated, %:
C 71.03; H 9.66; N 4.36.
N-Methyl-N-benzylammonium exo-2-hydroxy-5-
oxo-4-oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxy-
late (XII). Yield 0.50 g (79%), mp 164–166°C, Rf 0.13
(B). IR spectrum, cm–1: 3400, 2550, 1790, 1735, 1675,
exo-2-Hydroxy-5-oxo-4-oxatricyclo-[4.2.1.03,7]-
nonane-endo-9-carboxylic acid (X). a. The compound
was obtained by procedure used in oxidation of amido
acids (see further) from anhydride I, amide IIb and IId,
or acid III. Yields 0.33 g (83%), 0.28 g (70%), 0.34 g
(85%), and 0.38 g (96%) respectively, mp 200–202°C
(from acetone) (202–203°C [25]), Rf 0.10 (A), 0.58 (B).
IR spectrum, cm–1: 3400, 1766, 1726, 1412, 1324, 1198,
1060, 1036, 1006. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 12.56 br.s (1H, COOH), 5.24 br.s (1H, OH),
1
1600, 1410, 1365, 1220, 1175, 1030, 765. H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 8.23 br.s (2H,
H2N+), 7.46–7.21 (5Harom), 6.78 br.s (1H, OH), 4.44 s
3
(2H, CH2), 4.31 d (1H, H3, J3,7 5.1 Hz), 4.05 C (1H,
3
H2), 3.18 m (1H, H7), 3.02 d.d (1H, H9, J9,1 3.0,
3J6,9 10.5 Hz), 2.64 d.d (1H, H6, 3J6,7 4.5 Hz), 2.63 s (3H,
CH3), 2.42 br.s (1H, H1), 1.96 d (1H, H8s), 1.50 d (1H,
H8an, 2J8s,8an 11.0 Hz). Found, %: C 63.88; H 6.61; N 4.40.
C17H21NO5. Calculated, %: C 63.95; H 6.58; N 4.39.
Dibenzylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XIII). Yield 0.66 g (83%), mp 101–104°C, Rf 0.38 (B).
IR spectrum, cm–1: 3415, 2640, 1780, 1735, 1600, 1360,
3
4.31 d (1H, H3, J3,7 5.0 Hz), 4.01 s (1H, H2), 3.19 m
3
3
(1H, H7), 3.04 d.d (1H, H9, J6,9 10.8, J9,1 3.8 Hz),
2.66 d.d (1H, H6, 3J6,7 4.5 Hz), 2.41 br.s (1H, H1), 1.95 d
(1H, H8s), 1.50 d (1H, H8a, 2J8s,8a 10.7 Hz).
1
1220, 1175, 1030, 765. H NMR spectrum (300 MHz,
b. To a solution of 0.61 g (2 mmol) of salt XVII in
15 ml of water 0.33 ml (2 mmol) of 20% solution of
hydrochloric acid was added, and the mixture obtained
was evaporated in a vacuum. The solid residue was
treated with hot acetone, and the benzylamine hydro-
chloride was filtered off. On cooling the acetone filtrate
crystals of compound X precipitated. Yield 0.20 g (51%).
DMSO-d6), δ, ppm: 8.30 br.s (2H, H2N+), 7.43–
7.30 (10Harom), 4.35 br.s (1H, OH), 4.30 d (1H, H3,
3J3,7 4.8 Hz), 4.07 s (1H, H2), 3.89 s (4H, 2CH2), 3.16 m
(1H, H7), 2.99 d.d (1H, H9, J9,1 2.4, J6,9 10.5 Hz),
2.62 d.d (1H, H6, 3J6,7 4.5 Hz), 2.41 br.s (1H, H1), 1.94 d
(1H, H8s), 1.48 d (1H, H8an, 2J8s,8an 10.5 Hz). Found, %:
C 69.91; H 6.40; N 3.49. C23H25NO5. Calculated, %:
C 69.87; H 6.33; N 3.54.
3
3
Oxidation of amido acids of norbornene series with
performic acid in situ. To 2 mmol of an appropriate
amido acid IIa–IIj in 5–8 ml of 98% formic acid was
added dropwise while stirring at 0°C 0.23 ml (4 mmol)
of 50% water solution of hydrogen peroxide, and the
stirring at this temperature was continued till the
completion of the reaction (TLC monitoring). The formic
Dipropylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XIV). Yield 0.48 g (81%), oily substance, Rf 0.25 (B).
IR spectrum, cm–1: 3400, 2560, 1785, 1600, 1355, 1210,
1170, 1030, 770. 1H NMR spectrum (200 MHz, DMSO-
d6), δ, ppm: 8.38 br.s (2H, H2N+), 4.22 d (1H, H3,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
671
3J3,7 5.6 Hz), 4.09 s (1H, H2), 3.08 m (1H, H7), 2.82 d.d
of hydrogen peroxide, and the stirring at this temperature
was continued till the completion of the reaction (TLC
monitoring). The formic acid was removed in a vacuum,
ethyl ether was added to the oily residue, and after
prolonged grinding in the cold the formed crystals were
filtered off and dried. Yield 0.45 g (74%).
3
3
(1H, H9, J9,1 3.0, J6,9 10.8 Hz), 2.73 t (4H, 2CH2),
2.48 d.d (1H, H6, 3J6,7 4.8 Hz), 2.33 br.s (1H, H1), 1.88 d
(1H, H8s), 1.67–1.48 m (4H, 2CH2), 1.40 d (1H, H8an
,
2J8s,8an 10.4 Hz), 0.86 t (6H, 2CH3). Found, %: C 60.23;
H 8.40; N 4.60. C15H25NO5. Calculated, %: C 60.20;
H 8.36; N 4.68.
c. To 0.54 g (2 mmol) of amido acid IIc dissolved in
a mixture of dichloromethane and acetonitrile (3:1 v/v)
was added dropwise while stirring at 0°C 0.15 ml
(4 mmol) of 98% formic acid and 0.23 ml (4 mmol) of
50% water solution of hydrogen peroxide, and the stirring
at this temperature was continued till the completion of
the reaction (TLC monitoring). The volatile substances
were removed in a vacuum. After a usual workup we
obtained the target product in 0.43 g (71%) yield.
Diisopropylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XV). Yield 0.40 g (67%), oily substance, Rf 0.12 (B).
IR spectrum, cm–1: 3400, 2495, 1785, 1720, 1600, 1360,
1
1220, 1180, 1030, 770. H NMR spectrum (200 MHz,
DMSO-d6), δ, ppm: 8.34 br.s (2H, H2N+), 4.86 br.s (1H,
OH), 4.27 d (1H, H3, 3J3,7 5.4 Hz), 4.03 s (1H, H2),
3
3
3.52 d.d (1H, H9, J9,1 4.2, J6,9 10.6 Hz), 3.14 m (1H,
H7), 3.00 m (2H, 2CH), 2.57 d.d (1H, H6, 3J6,7 4.5 Hz),
2.37 br.s (1H, H1), 1.98 d (1H, H8s), 1.55 d (1H, H8an
d. To 0.54 g (2 mmol) of amido acid IIc in 8 ml of
glacial acetic acid was added dropwise while stirring
at room temperature (17°C) 0.23 ml (4 mmol) of 50%
water solution of hydrogen peroxide, and the stirring at
this temperature was continued till the completion of the
reaction (TLC monitoring). The acetic acid was removed
in a vacuum. After a usual workup we obtained the target
product in 0.43 g (70%) yield.
,
2J8s,8an 11.4 Hz), 1.20 d (12H, 4CH3). Found, %: C 60.16;
H 8.41; N 4.70. C15H25NO5. Calculated, %: C 60.20;
H 8.36; N 4.68.
Dipentylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XVI). Yield 0.46 g (65%), mp 99–101°C, Rf 0.44 (B).
IR spectrum, cm–1: 3398, 2550, 1774, 1724, 1586, 1410,
Mixture of diethylammonium exo-2-hydroxy-5-
oxo-4-oxatricyclo-[4.2.1.03,7]nonane-endo-9-
carboxylate (XVIII) (50%) with exo-2-hydroxy-5-oxo-
4-oxatricyclo[4.2.1.03,7]nonane-endo-9-carboxylic
acid (X) (50%). Yield 0.35 g (74%), Rf 0.12 and 0.58 (B).
IR spectrum, cm–1: 3300, 3185, 2650, 1785, 1725, 1585,
1
1350, 1200, 1168, 1016, 763. H NMR spectrum (200
MHz, DMSO-d6), δ, ppm: 7.35 br.s (2H, H2N+), 4.24 d
(1H, H3, 3J3,7 5.6 Hz), 4.10 s (1H, H2), 3.10 m (1H, H7),
3
3
2.87 d.d (1H, H9, J9,1 3.2, J6,9 10.6 Hz), 2.74 t (4H,
2CH2), 2.51 d.d (1H, H6, J6,7 3.7 Hz), 2.35 br.s (1H,
3
H1), 1.90 d (1H, H8s), 1.63–1.48 m (4H, 2CH2), 1.43 d
1
1360, 1240, 1170, 1025, 765. H NMR spectrum
(1H, H8an, J8s,8an 10.8 Hz), 1.29–1.22 m (8H, 4CH2),
2
(200 MHz, DMSO-d6), δ, ppm: 7.50 br.s (2H, H2N+),
6.30 br.s (2H, OH), 4.23 d (2H, H3, 3J3,7 5.1 Hz), 4.14 s (2H,
H2), 3.10 m (2H, H7), 2.81 d.d (2H, H9, 3J6,9 10.8 Hz),
0.86 t (6H, 2CH3). Found, %: C 64.16; H 9.31; N 4.00.
C19H33NO5. Calculated, %: C 64.23; H 9.30; N 3.94.
3
2.81 q (4H, 2CH2), 2.49 d.d (2H, H6, J6,7 3.9 Hz),
Benzylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XVII). a. Yield 0.46 g (75%), mp 139–140.5°C, Rf 0.20
(B). IR spectrum, cm–1: 3212, 3014, 1766, 1724, 1604, 1368,
1180, 1014, 788. 1H NMR spectrum (300 MHz, DMSO-
d6), δ, ppm: 8.34 br.s (3H, H3N+), 7.47–7.27 (5Harom),
5.34 br.s (1H, OH), 4.28 d (1H, H3, 3J3,7 5.1 Hz), 4.06 s
(1H, H2), 4.00 s (2H, CH2), 3.14 m (1H, H7), 2.95 d.d
2.34 br.s (2H, H1), 1.89 d (2H, H8s), 1.41 d (2H, H8an
,
2J8s,8an 10.7 Hz), 1.14 t (6H, 2CH3). 1H NMR spectrum
(200 MHz, CDCl3), δ, ppm: 8.47 br.s (2H, H2N+), 4.45 d
3
(2H, H3, J3,7 4.8 Hz), 4.26 s (2H, H2), 4.13 br.s (2H,
OH), 3.22 m (2H, H7), 2.97 d.d (2H, H9, 3J6,9 10.1 Hz),
3
2.97 q (4H, 2CH2), 2.63 d.d (2H, H6, J6,7 4.1 Hz),
2.63 br.s (2H, H1), 2.12 d (2H, H8s), 1.56 d (2H, H8an
,
3
3
(1H, H9, J9,1 3.2, J6,9 10.5 Hz), 2.59 d.d (1H, H6,
3J6,7 5.1 Hz), 2.39 br.s (1H, H1), 1.93 d (1H, H8s), 1.46 d
(1H, H8an, 2J8s,8an 10.8 Hz). Found, %: C 62.88; H 6.29;
N 4.63. C16H19NO5. Calculated, %: C 62.95; H 6.23;
N 4.59.
2J8s,8an 11.0 Hz), 1.31 t (6H, 2CH3).
Diethylammonium exo-2-hydroxy-5-oxo-4-
oxatricyclo-[4.2.1.03,7]nonane-endo-9-carboxylate
(XVIII). a. To 0.47 g (2 mmol) of amido acid IIg in 8 ml
of glacial acetic acid was added dropwise at room
temperature (20°C) while stirring 0.23 ml (4 mmol) of
50% water solution of hydrogen peroxide, and the stirring
at this temperature was continued till the completion of
b. To a solution of 0.54 g (2 mmol) of amido acid IIc
in 8 ml of 98% formic acid was added dropwise while
stirring at 0°C 0.45 ml (8 mmol) of 50% water solution
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

PAL’CHIKOV et al.
672
the reaction (TLC monitoring). The acetic acid was
removed in a vacuum. After a usual workup we obtained
the target product in 0.34 g (63%) yield, mp 147–150°C,
Rf 0.12 (B). IR spectrum, cm–1: 3390, 2530, 1780, 1595,
10 ml of anhydrous dichloromethane at 0°C was added
while stirring 0.21 ml (2 mmol) of freshly distilled
diethylamine and a solution of 0.41 g (2 mmol) of
dicyclohexylcarbodiimide in 5 ml of anhydrous dichloro-
methane. After stirring for 4 days the precipitate of
dicyclohexylurea was filtered off. The filtrate was
evaporated in a vacuum, the residue was ground under
a layer of ethyl ether, the formed crystals were filtered
off, washed with ether, and recrystallized from 2-pro-
panol. Yield 0.39 g (78%), mp 161–163.5°C, Rf 0.45 (B).
IR spectrum, cm–1: 3420, 1800, 1620, 1460, 1150, 1085,
1030. 1H NMR spectrum (300 MHz, DMSO-d6), δ, ppm:
1
1415, 1360, 1220, 1180, 1030, 775. H NMR spec-
trum (300 MHz, DMSO-d6), δ, ppm: 7.50 br.s (2H,
H2N+), 6.30 br.s (1H, OH), 4.23 d (1H, H3, 3J3,7 5.1 Hz),
4.15 s (1H, H2), 3.10 m (1H, H7), 2.81 d.d (1H, H9,
3J6,9 10.8 Hz), 2.81 q (4H, 2CH2), 2.49 d.d (1H, H6,
3J6,7 3.9 Hz), 2.34 br.s (1H, H1), 1.89 d (1H, H8s), 1.41 d
(1H, H8an, 2J8s,8an 10.7 Hz), 1.14 t (6H, 2CH3).
b. To 0.47 g (2 mmol) of amido acid IIg in 10 ml of
chloroform was added 0.34 g (4 mmol) of sodium
hydrogen carbonate, then dropwise was added at stirring
0.38 ml (4 mmol) of freshly distilled acetic anhydride
and 0.23 ml (4 mmol) of 50% water solution of hydrogen
peroxide, and the stirring at room temperature (20°C)
was continued till the completion of the reaction (TLC
monitoring). The volatile substances were removed in a
vacuum. After a usual workup we obtained the target
product in 0.35 g (65%) yield.
3
5.07 s (1H, OH), 4.29 d (1H, H3, J3,7 5.1 Hz), 4.43 s
(1H, H2), 3.32 q (2H, CH2), 3.19 m (1H, H7), 3.15 d.d
3
3
(1H, H9, J9,1 3.9, J6,9 10.2 Hz), 3.12 q (2H, CH2),
2.68 d.d (1H, H6, 3J6,7 4.8 Hz), 2.29 br.s (1H, H1), 1.96 d
(1H, H8s), 1.52 d (1H, H8an, 2J8s,8an 10.5 Hz), 1.13 t (3H,
CH3), 0.96 t (3H, CH3). Found, %: C 61.71; H 7.48;
N 5.49. C13H19NO4. Calculated, %: C 61.66; H 7.51;
N 5.53.
b. To a mixture of 0.40 g (2 mmol) of lactonoacid X
in 5 ml of anhydrous acetone was added 0.21 ml (2 mmol)
of freshly distilled diethylamine. The mixture was stirred
at room temperature for 24 h. The reaction product was
filtered off, washed with a little anhydrous acetone, and
dried. To the dispersion of 0.54 g (2 mmol) of obtained
salt XV in 10 ml of anhydrous dichloromethane was
added at 0°C while stirring a solution of 0.41 g (2 mmol)
of dicyclohexylcarbodiimide in 5 ml of anhydrous
dichloromethane.After stirring for 4 days the precipitate
of dicyclohexylurea was filtered off. The filtrate was
evaporated in a vacuum to dryness, the residue was
ground under a layer of ethyl ether, the formed crystals
were filtered off, washed with ether, and recrystallized
from 2-propanol. Yield 0.49 g (96%).
c. A mixture of 0.47 g (2 mmol) of amido acid IIg,
1.16 g (4 mmol) of 54% m-chloroperbenzoic acid in
15 ml of anhydrous dichloromethane was stirred at room
temperature for 48 h till the completion of the reaction
(TLC monitoring). The formed m-chlorobenzoic acid was
neutralized with a saturated water solution of sodium
carbonate. The water layer was separated, evaporated in
air at room temperature, the solid residue was treated
with a solvent mixture chloroform–acetonitrile–2-
propanol, 1:1:1 by volume, the solution was filtered, and
the solvent was removed in a vacuum. After a usual
workup we obtained the target product in 0.17 g (31%)
yield.
d. A mixture of 0.47 g (2 mmol) of amido acid IIg,
0.06 g (1 mmol) of urea, 1.12 g (4 mmol) of freshly
prepared 65% monoperoxyphthalic acid in 20 ml of ethyl
acetate was stirred at room temperature for 48 h till the
completion of the reaction (TLC monitoring). The formed
phthalic acid was neutralized with a saturated water
solution of sodium carbonate. The water layer was
separated, evaporated in air at room temperature, the solid
residue was treated with a solvent mixture chloroform–
acetonitrile–2-propanol, 1:1:1 by volume, the solution
was filtered, and the solvent was removed in a vacuum.
After a usual workup we obtained the target product in
0.27 g (49%) yield.
N,N-Dipentyl-exo-2-hydroxy-5-oxo-4-oxatri-
cyclo[4.2.1.03,7]nonane-endo-9-carboxamide (XXII).
To a solution of 0.71 g (2 mmol) of salt XVI in 15 ml of
anhydrous dichloromethane was added at room tempera-
ture while stirring a solution of 0.41 g (2 mmol) of
dicyclohexylcarbodiimide in 5 ml of anhydrous
dichloromethane.After stirring for 4 days the precipitate
of dicyclohexylurea was filtered off. The filtrate was
evaporated in a vacuum to dryness, the residue was
ground under a layer of ethyl ether, the formed crystals
were filtered off, washed with ether, and dried. The
evaporation of the ether filtrate to 1/3 of its volume
provided a second portion of the reaction product. The
combined product was recrystallized from 2-propanol.
N,N-Diethyl-exo-2-hydroxy-5-oxo-4-oxa-
tricyclo[4.2.1.03,7]nonane-endo-9-carboxamide (XXI).
a. To a mixture of 0.40 g (2 mmol) of lactonoacid X and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

LACTONATION OF N-ALKYL- AND N,N-DIALKYLAMIDO ACIDS
673
Yield 0.36 g (53%), mp 110–112°C, Rf 0.82 (B). 1H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 5.07 d (1H,
14. Tarabara, I.N., Kas’yan, A.O., Krishchik, O.V., Shishki-
na, S.V., Shishkin, O.V., and Kas’yan, L.I., Zh. Org. Khim.,
2002, vol. 38, p. 1354.
15. Kas’yan, L.I., Krishchik, O.V., Tarabara, I.N., Kas’-
yan, A.O., and Pal’chikov, V.A., Zh. Org. Khim., 2006,
vol. 42, p. 519.
16. Kometani, T., Fitz, T., and Watt, D.S., Tetrahedron Lett.,
1986, vol. 27, p. 919.
17. Zefirov, N.S. and Sokolov, V.I., Usp. Khim., 1967, vol. 36,
p. 243.
3
OH, JOH,2 3.6 Hz), 4.41 d (1H, H2), 4.29 d (1H, H3,
3J3,7 5.1 Hz), 3.19 t (2H, CH2), 3.17 m (1H, H7), 3.16 t
3
3
(2H, CH2), 3.02 d.d (1H, H9, J9,1 3.3, J6,9 10.2 Hz),
2.65 d.d (1H, H6, 3J6,7 5.0 Hz), 2.28 br.s (1H, H1), 1.96 d
(1H, H8s), 1.53 d (1H, H8an, 2J8s,8an 10.4 Hz), 1.28 m (12H,
6CH2), 0.87 t (6H, 2CH3). Found, %: C 67.69; H 9.16;
N 4.12. C19H31NO4. Calculated, %: C 67.66; H 9.20;
N 4.15.
18. Nakanisi, K., IR Spectra and Organic Compounds
Structure, Moscow: Mir, 1965, 210 p.
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