Study of ring cleavage in quaternary ammonium salts of 1,3-diazaadamantane

Article abstract of DOI:10.1007/s11172-007-0242-6

A series of quaternary ammonium salts of 5,7-dimethyl-1,3-diazaadamantan-6- one bearing aryl and alkyl substituents was synthesized. On treatment with aqueous KOH, these compounds undergo ring cleavage to give 3,7-diazabicyclo[3.3. 1]nonane derivatives. T

Full text of DOI:10.1007/s11172-007-0242-6

Russian Chemical Bulletin, International Edition, Vol. 56, No. 8, pp. 1555—1560, August, 2007
1555
Study of ring cleavage in quaternary ammonium salts
of 1,3ꢀdiazaadamantane*
S. Z. Vatsadze,ꢀ V. S. Semashko, M. A. Manaenkova, and N. V. Zyk
Department of Chemistry , Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 932 8846. Eꢀmail: szv@org.chem.msu.ru
A series of quaternary ammonium salts of 5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀone bearꢀ
ing aryl and alkyl substituents was synthesized. On treatment with aqueous KOH, these comꢀ
pounds undergo ring cleavage to give 3,7ꢀdiazabicyclo[3.3.1]nonane derivatives. The product
1
structure was confirmed by H and 13C NMR and IR spectroscopy.
Key words: quaternary ammonium salts, 5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀone, ring
cleavage.
Scheme 1
The design and synthesis of molecules capable of selfꢀ
assembly is an important trend in modern chemistry. The
selfꢀassembly principle underlies many biological proꢀ
cesses, giving rise to nanosystems of a definite structure
(the best known selfꢀassembling system is DNA).1,2 From
the standpoint of organic chemistry, selfꢀassembly is based
on noncovalent (secondary) interactions2 (hydrogen
bonds, πꢀstacking, charge transfer complexes, hydrophoꢀ
bic interactions, coordination bonds, and van der Waals
interactions).
The use of selfꢀassembly principle opens up broad
prospects for the preparation of nanostructures with unique
properties. Apart from simulation of biological processes,
this allows one to obtain molecular devices, sensor mateꢀ
rials, which change their properties depending on the exꢀ
ternal action (photo, chemical, electrical, and mechaniꢀ
cal),3 liquid crystals, polymer and gel solutions used in
modern optics, electronics, and so on.4,5
tion—gel transition in the metal—ligand systems containꢀ
ing two different metals (lanthanum or europium + coꢀ
balt or zinc as metals and 2,6ꢀbis(benzimidazolyl)pyridine
derivatives as ligands) has been studied.6 This furnished
thermally and mechanically sensitive gels.
3,7ꢀDiazabicyclo[3.3.1]nonanes (bispidines) are bioꢀ
logically active compounds.7 For example, 9ꢀoxo deꢀ
rivatives exhibit analgesic activity,8 and unsymmetrical
Nꢀsubstituted diazabicyclononanes are used as antiꢀ
arrhythmic drugs.9
In our opinion, of most interest is the preparation of
coordination polymers based on selfꢀassembly where bindꢀ
ing of a metal to a polydentate ligand is the driving force
of the process (Scheme 1). These supramolecular strucꢀ
tures combine the properties introduced by both the metal
ion and the organic ligand. Depending on the ligand
denticity and the metal coordination number and coordiꢀ
nation environment, this may give diverse supramolecuꢀ
lar assemblies (linear chains, branched twoꢀdimensional
The 3,7ꢀdiazabicyclo[3.3.1]nonane system is also of
interest for coordination chemistry, as this ligand can
form stable chelates with metals.10
By connecting two bispidine fragments by a bridge,
one can obtain a ligand able to form coordination polyꢀ
mers of diverse geometry depending on the linker type
and the mode of connection of chelating groups to each
other. This brings about the task of synthesizing various
substituted 3,7ꢀdiazabicyclo[3.3.1]nonanes, including
unsymmetrical N,N´ꢀdisubstituted derivatives. For the
preparation of ditopic ligands (see Scheme 1) bridging of
positions 9 of two bicyclononane cages appears most effiꢀ
networks, threeꢀdimensional frameworks, etc.)3,4
.
The studies dealing with preparation of phases with
reversible solution—gel (or sol—gel) transition are of inꢀ
terest in this field. For example, the reversible soluꢀ
* Dedicated to Academician V. A. Tartakovsky on occasion of
his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1496—1501, August, 2007.
1066ꢀ5285/07/5608ꢀ1555 © 2007 Springer Science+Business Media, Inc.

1556
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Vatsadze et al.
cient. Hence, convenient methods for 9ꢀfunctionalization
of 3,7ꢀdiazabicyclo[3.3.1]nonane are required.
On treatment with a fivefold excess of KOH in water
for 12 h, all salts 1b—d underwent ring cleavage to give
unsymmetrically Nꢀsubstituted 3,7ꢀdiazabicyclo[3.3.1]noꢀ
nanes; however, the product composition and yields were
different. Thus the transformation of compound 1a gave a
precipitate of only Nꢀformyl derivative 2a in 72% yield; in
the case of compound 1b, the precipitate was a mixture of
Nꢀformylꢀ (2b) and Nꢀunsubstituted product (3b) in 2 : 1
molar ratio (Scheme 3) (yields 40% and 16%, respecꢀ
tively, calculated relative to the pure product).
This study starts a series of works on the use of
3,7ꢀdiazabicyclo[3.3.1]nonane systems as new ligands for
the preparation of metal gels. Previously,11 we discovered
a new method for the synthesis of unsymmetrical N,Nꢀdiꢀ
substituted 3,7ꢀdiazabicyclo[3.3.1]nonane derivatives
bearing the 9ꢀhydroxy group. The ring cleavage reacꢀ
tion of 1ꢀbenzylꢀ5,7ꢀdimethylꢀ6ꢀoxoꢀ1ꢀazoniaꢀ3ꢀazaadaꢀ
mantane chloride (1a) induced by aqueous alkali results
in the stereoselective formation of antiꢀ7ꢀbenzylꢀ3ꢀ
formylꢀ1,5ꢀdimethylꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀol
(2a) (Scheme 2).
Scheme 3
Scheme 2
Reagents and conditions: 5 KOH, H2O, 12 h.
Reagents and conditions: 5 KOH, H2O, 12 h.
Salt 1a and its analogs are promising as the initial
compounds for the synthesis of various unsymmetrically
substituted 3,7ꢀdiazabicyclo[3.3.1]nonanes. Here we studꢀ
ied substrates that can be involved in such processes and
specific features of this reaction for each of the substrates.
In both cases, the mother liquors contained two prodꢀ
ucts (Nꢀformylꢀsubstituted derivative 2a or 2b and Nꢀunꢀ
substituted derivative 3a or 3b); in the case of salt 1a, the
former compound predominated, while for salt 1b, the
latter one was predominant.
The ring cleavage in salt 1b carried out in the presence
of 5 equivalents of formaldehyde resulted in precipitation
of only Nꢀformyl derivative 2b, the product yield being
increased to 95%.
In the case of alkyl salts 1c and 1d, cleavage (Scheme 4)
did not give Nꢀformyl derivatives at all. Probably, the
intermediate hemiaminal was rapidly hydrolyzed under
these conditions (the presumptive reaction mechanism is
Results and Discussion
As a continuation of previous work,11 we prepared a
number of salts of 5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀ
one with various substituents at the quaternary nitrogen
atom (aromatic or aliphatic).
These were 5,7ꢀdimethylꢀ1ꢀ
(2ꢀnitrobenzyl)ꢀ6ꢀoxoꢀ3ꢀazaꢀ1ꢀ
azoniaadamantane bromide (1b),
Scheme 4
5,7ꢀtrimethylꢀ6ꢀoxoꢀ3ꢀazaꢀ1ꢀ
azoniaadamantane iodide (1c),
and 5,7ꢀdimethylꢀ1ꢀpropylꢀ6ꢀ
oxoꢀ3ꢀazaꢀ1ꢀazoniaadamantane
iodide (1d).
1
b
c
d
R
oꢀNO2Ph
H
X
Br
I
This selection of salts with
various groups at the quaternary
nitrogen atom provides the posꢀ
sibility of elucidating the subꢀ
CH2Me
I
stituent effect on the reaction and obtaining various
diazabicyclononanes with aromatic and aliphatic substituꢀ
ents at nitrogen atoms.
Reagents and conditions: 5 KOH, H2O, 12 h.
R = H (1c, 3c, 4c), CH2Me (1d, 3d, 4d)

Ring cleavage of 1,3ꢀdiazaadamantane salts
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1557
shown in Scheme 5) and, hence, the reduction of the
carbonyl group in position 9 became impossible.
has been reported12 that the rates of anionic rearrangeꢀ
ments with hydride transfer depend on the cation.
In both cases, the reaction products did not precipiꢀ
tate but remained in solution as a finely dispersed suspenꢀ
sion and could be isolated by chloroform extraction. The
formation of these products was confirmed by 1H and
13C NMR and IR spectroscopy data.
Compound 3c or 3d containing a 9ꢀoxo group preꢀ
dominated in both cases. The rate of ring cleavage reacꢀ
tion was lower for alkyl salts than for benzyl salts. In the
order of decreasing reaction rate, these salts can be arꢀ
ranged in the sequence: 1b > 1a > 1c > 1d. In the lastꢀ
mentioned case, the reaction was not completed even in
several days, and the aqueous phase after extraction conꢀ
tained a considerable amount of the unreacted salt.
In all cases of ring cleavage reactions, the replacement
of KOH by NaOH did not cause any changes, although it
Previously, we determined11 the structure of comꢀ
pound 2a by NMR and Xꢀray diffraction analysis. The
1H NMR spectra of compounds 2b and 2a are similar.
When the reaction of 1a with 1 equiv. of KOH was
carried out in a twoꢀphase H2O—CHCl3 system (2 : 3 v/v),
product 3a containing no alcohol or formyl group was
isolated from the organic phase in 48% yield11 (Scheme 6).
Scheme 6
Scheme 5
Reagents and conditions: 1 KOH, H2O/CHCl3, 1 h.
In addition, treatment with concentrated HCl afforded
the product of hydrolysis of compound 2a, 1,5ꢀdimethylꢀ
3ꢀbenzylꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀol (4a), in
73% yield (Scheme 7).11
Scheme 7
The product mixtures obtained in the reactions acꢀ
cording to Schemes 3 and 4 were identified by compariꢀ
son with the spectra of benzyl derivatives (see Scheme 2).
1
Figure 1 shows the H NMR spectra (in CDCl3) for
the product mixture formed according to Scheme 3 and
product 2a (see Scheme 2).
The NMR spectra of the reaction products formed
according to Scheme 4 exhibit two sets of signals. The
pattern of signals (multiplicity and chemical shifts) obꢀ
served for the bicyclic cage resembles that observed in the
spectra of known benzyl analogs (2a,b, 3b,a, 4a). For
illustration, Fig. 2 shows the 13C NMR spectrum of a
product mixture formed from diazaadamantane salt 1c (in
DMSOꢀd6).
Thus, we found that ring cleavage in quaternary
diazaadamantane salts having a benzyl substituent afꢀ

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Vatsadze et al.
v
*
a
v
*
v
*
v
v
v
v
v
v
v
*
*
*
*
8
7
6
5
4
3
2
δ
b
8
7
6
5
4
3
2
δ
Fig. 1. (a) 1H NMR spectrum of a mixture of 2b and 3b (the signals of 2b are ticked and the signals for 3b are asterisked, the signals for
aromatic protons are omitted); (b) spectrum of compound 2a. In both cases, CDCl3 served as the solvent. Detailed signal assignment
is given in the Experimental.
*
*
*
*
v
v
v
*
v
v
v
*
200
180
160
140
120
100
80
60
40
δ
Fig. 2. 13C NMR spectrum of a mixture of products 3c and 4c (in DMSOꢀd6). The signals of compound 3c are asterisked and the
signals of compound 4c are ticked. Detailed signal assignment is given in the Experimental.
spectrometer operating at 400 MHz at 28 °C. The chemical
shifts are referred to internal HMDS. IR spectra were measured
on URꢀ20 (in thin film or Nujol) and Specord 75 IR instruments
(Nujol). The melting points were determined in block in an
open capillary and were not corrected. Elemental analysis of the
compounds was carried out on a CarloꢀErba CРТ analyzer.
fords mainly Nꢀformylꢀsubstituted bispidines with the
9ꢀhydroxy group, whereas in the presence of an alkyl
substituent, bispidine with the 9ꢀoxo group is formed as
the major product.
The results of further studies on the dependence of the
reactivity of substrates and reaction pathways on the subꢀ
stituent at the quaternary nitrogen atom will be published
elsewhere.
Preparation of quaternary ammonium salts of
5,7ꢀdimethylꢀ1,3ꢀdiazaadamantane
Experimental
1ꢀBenzylꢀ5,7ꢀdimethylꢀ6ꢀoxoꢀ3ꢀazaꢀ1ꢀazoniaadamantane
chloride (1a). Benzyl chloride (2.11 g, 0.016 mol) was added to
a solution of 5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀone (3 g,
The reagents and solvents were purified by standard proceꢀ
dures.13 1H NMR spectra were recorded on a Bruker Avanceꢀ400

Ring cleavage of 1,3ꢀdiazaadamantane salts
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1559
0.016 mol) in benzene (25 mL) and the mixture was refluxed
for 4 h. After cooling, the precipitate was filtered off, washed
with benzene, and recrystallized from chloroform to give 3.55 g
(70 %) of compound 1a, m.p. 239—242 °C (Ref. 14: m.p.
242—247 °C). The spectral characteristics were reported preꢀ
viously.11
product 2a. The spectral characteristics were reported preꢀ
viously.11
Ring cleavage of salt 1b by 5 equiv. KOH in water. Salt 1b
(1 g, 0.0025 mol) was placed in a solution of KOH (0.69 g,
0.012 mol) in H2O (12 mL). A yellow precipitate was formed
immediately. Water (12 mL) was added to the solution and the
mixture was stirred for 4 h. Then the mixture was additionally
diluted with water (70 mL) and kept for 16 h at 4 °C. The
yellowish precipitate was filtered off, washed with water and
ethanol, and dried. The precipitate (0.48 g) was a mixture of
products 2b and 3b (molar ratio 2 : 1; yields 40 and 16%, respecꢀ
5,7ꢀDimethylꢀ1ꢀ(oꢀnitrobenzyl)ꢀ6ꢀoxoꢀ1ꢀazaꢀ1ꢀazoniaadaꢀ
mantane bromide (1b). The procedure was similar to that deꢀ
scribed above except that benzyl chloride was replaced by
oꢀnitrobenzyl bromide (3.6 g, 0.016 mol). Yield 3.96 g (60%),
m.p. 240—242 °C. 1H NMR (DMSOꢀd6), δ: 0.85 (s, 6 H, 2 Me);
3.0 (d, 2 H, Hax(4), Hax(8), J = 12.3 Hz); 3.45 (d, 2 H, Heq(4),
Heq(8), J = 12.5 Hz); 3.73 (d, 2 H, Hax(9), Hax(10), J = 11.0 Hz);
3.82 (d, 2 H, Heq(9), Heq(10), J = 11.0 Hz); 4.77 (s, 2 H,
CH2Ar); 4.90 (s, 2 H, NCH2N); 7.79 (d, 1 H, CH(6)(Ar), J =
7.2 Hz); 7.80—7.91 (m, 2 H, CH(4), CH(5), Ar); 8.19 (d, 1 H,
CH(3), Ar, J = 7.8 Hz). 13C NMR (DMSOꢀd6), δ: 15.5 (Me);
45.5 (CMe); 60.0 (CH2Ar); 61.5 (C(4), C(8)); 64.5 (C(9),
C(10)); 79.0 (NCH2N); 120.0 (C1(Ar)); 126.5 (C3(Ar)); 133.0,
134.5 (C4(Ar), C6(Ar)); 137.0 (C5(Ar)); 151.0 (C2(Ar)); 206.0
(C=O). Found (%): C, 51.33; H, 5.62; N, 10.66. C17H22BrN3O3.
Calculated (%): C, 51.52; H, 5.56; N, 10.61.
1
tively). H NMR (CDCl3), δ: 0.85 (s, 3 H, 2 CH3 (3b)); 0.91,
0.93 (both s, 3 H each, 2 Me (2b)); 1.80 (d, 1 H, OH (2b), J =
4.7 Hz); 2.32 (dd, 1 H, Hax(6)/Hax(8) (2b), J = 11.2 Hz, J =
2.2 Hz); 2.38—2.60 (m, 5 H, CH2 (3b), (2b)); 2.80 (br.s, 1 H,
NH (3b)); 3.02 (d, 1 H, CH2 (3b), J = 11.9 Hz); 3.07 (d, 1 H,
Hax(2) (2b), J = 13.5 Hz); 3.22 (d, 1 H, CH2 (3b), J = 14.1 Hz);
3.30 (d, 1 H, H(9) (2b), J = 3.7 Hz); 3.43—3.55 (m, 3 H, H(10),
Heq(2) (2b), CH2 (3b)); 3.67 (s, 1H, CH2Ar (3b)); 3.75 (d, 1 H,
H(10) (2b), J = 14.9 Hz); 4.32 (d, 1 H, Heq(4) (2b), J = 13.5 Hz);
7.34—7.44, 7.46—7.53, 7.55—7.66, 7.83—7.91 (all m, 6 H each,
CH, Ar (2b, 3b)); 7.97 (s, 1 H, CHO (2b)).
1,5,7ꢀTrimethylꢀ6ꢀoxoꢀ1ꢀazaꢀ1ꢀazoniaadamantane iodide
(1c). Methyl iodide 8 g (0.056 mol) was added to a solution of
5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀone (10.15 g, 0.056 mol)
in dry EtOH (30 mL), and the flask was gently heated with
stirring for 15 min. Then EtOH (20 mL) was added and the
mixture was stirred for additional 15 min. The precipitate thus
formed was filtered off and recrystallized from alcohol. Cooling
of the mother liquor gave an additional product. The total yield
was 15.1 g (81%), m.p. 241—242 °C (Ref. 15: m.p. 240—241 °C).
1H NMR (DMSOꢀd6), δ: 0.9 (s, 6 H, 2 Me); 2.95 (s, 3 H,
N+CH3); 3.08, 3.38 (both d, 2 H each, H(9), H(10), J =
2.35 Hz); 3.82 (br.s, 4 H, H(4), H(8)); 4.78 (br.s, 2 H, NCH2N).
13C NMR (DMSOꢀd6), δ: 15.3 (CCH3); 45.1 (CMe); 48.8
(CH3N+); 61.4 (C(4), C(8)); 67.4 (C(9), C(10)); 79.1 (NCH2N);
206.9 (C=O). IR (Nijol), ν/cm–1: 1730 (C=O). Found (%):
C, 41.00; H, 5.93; N, 8.70. C11H29IN2O. Calculated (%):
C, 40.99; H, 5.90; N, 8.70.
Ring cleavage of salt 1b by 5 equiv. KOH in water in the
presence of formaldehyde. A solution (2.0 g, 0.005 mol) of salt 1b
in water (70 mL) was added to a solution of KOH (1.4 g,
0.025 mol) and formaldehyde (0.76 g, 0.025 mol) in water
(30 mL), and the mixture was stirred for 7 h at room temperaꢀ
ture. The yellowish precipitate was filtered off, washed with
water and ether, and dried to give 1.6 g (95%) of compound 2b,
m.p. 235—240 °C. Found (%): C, 61.36; H, 7.05; N, 12.34.
C17H23N3O4. Calculated (%): C, 61.25; H, 6.95; N, 12.60.
1H NMR (DMSOꢀd6), δ: 0.76, 0.77 (both s, 3 H each, 2 Me);
2.18—2.37 (m, 4 H, H(6), H(8)); 2.50 (d, 1 H, Hax(4), J =
13.8 Hz); 3.02 (d, 1 H, Hax(2), J = 13.5 Hz); 3.15 (d, 1 H, H(9),
J = 5.1 Hz); 3.39 (d, 1 H, CH2Ar, J = 14.9 Hz); 3.54 (d, 1 H,
Heq(2), J = 11.7 Hz); 3.60 (d, 1 H, CH2Ar, J = 15.2 Hz); 4.09
(d, 1 H, Heq(4), J = 13.9 Hz); 4.98 (d, 1 H, OH, J = 5.1 Hz);
7.46—7.56 (m, 1 H, H(Ar)); 7.65—7.70 (m, 2 H, H(Ar));
7.85—7.95 (m, 2 H, H(Ar), CHO).
5,7ꢀDimethylꢀ6ꢀoxoꢀ1ꢀpropylꢀ1ꢀazaꢀ1ꢀazoniaadamantane
iodide (1d). Propyl iodide (8.5 g, 0.05 mol) was added to a solution
of 5,7ꢀdimethylꢀ1,3ꢀdiazaadamantanꢀ6ꢀone (9 g, 0.05 mol) in
dry benzene (150 mL). The mixture was refluxed for ~5 h; after
cooling, the precipitate was filtered off, washed with benzene,
and dried. Yield 9.9 g (57%) (from CHCl3), m.p. 184—185 °C
(dec.). 1H NMR (CDCl3), δ: 1.00—1.12 (m, 9 H, 3 Me);
1.75—1.85 (m, 2 H, MeCH2CH2); 2.98 (d, 2 H, Hax(4), Hax(8),
J = 14.6 Hz); 3.57 (d, 2 H, Hax(9), Hax(10), J = 11.5 Hz);
3.65—3.73 (m, 2 H, MeCH2CH2); 3.90 (d, 2 H, Heq(4), Heq(8),
J = 12.7 Hz); 4.45 (d, 2 H, Heq(9), Heq(10), J = 12.0 Hz); 5.48
(s, 2 H, NCH2N). Found (%): C, 44.48; H, 6.64; N, 8.18.
C13H23N2OI. Calculated (%): C, 44.57; H, 6.57; N, 8.00.
Ring cleavage of salts 1c, 1d by 5 equiv. KOH in water (genꢀ
eral procedure). A solution of the salt (0.005 mol) and KOH
(1.5 g, 0.0025 mol) in water (35 mL) was stirred for ~35 h. The
reaction mixture was extracted with chloroform, and the extract
was dried over anhydrous Na2SO4 and concentrated to dryness.
The yellowish oil thus formed was analyzed.
Ring cleavage of salt 1c. Mixture of products 3c and 4c
(0.48 g, molar ratio 3 : 1, yields 40 and 13%, respectively).
1
IR (film), ν/cm–1: 1715 (C=O (3c)). H NMR (DMSOꢀd6), δ:
0.66 (s, 2 H, 2 Me (4c)); 0.75 (s, 6 H, 2 Me (3c)); 2.03 (s, 1 H,
NCH3 (4c)); 2.11 (s, 3 H, NCH3 (3c)); 2.19—2.25 (m, 2.66 H,
Hax(2), Hax(4) (3c), Hax(2), Hax(4) (4c)); 2.32 (d, 0.66 H, Heq(2),
Heq(4) (4c), J = 10.8 Hz); 2.36 (dd, 0.66 H, Hax(6), Hax(8) (4c),
J = 13.7 Hz, J = 2.7 Hz); 2.57 (dd, 2 H, Hax(6), Hax(8) (3c), J =
13.9 Hz, J = 2.7 Hz); 2.77 (d, 0.66 H, Heq(6), Heq(8) (4c), J =
13.9 Hz); 2.97 (br.s, 0.33 H, H(9) (4c)); 3.11 (d, 2 H, Heq(2),
Heq(4) (3c), J = 11.7 Hz); 3.24 (d, 2 H, Heq(6), Heq(8) (3c), J =
13.7 Hz); 4.70 (br.s, 0.33 H, NH (4c)). 13C NMR (DMSOꢀd6),
δ: 17.5 (CH3C (3c)); 21.5 (CH3C (4c)); 36.5 (MeC (4c)); 45.1
(MeC (3c)); 46.5 (NCH3 (4c)); 49.0 (NCH3 (3c)); 59.5, 60.5
(CH2 (4c)); 63.2, 68.8 (CH2 (3c)); 76.5 (COH, (4c)); 210.5
(C=O (3c)).
Ring cleavage reactions of the salts
Ring cleavage of salt 1a by 5 equiv. KOH in water. Comꢀ
pound 1a (1.2 g, 0.0039 mol) was added to a solution of KOH
(1 g, 0.020 mol) in H2O (20 mL) and the mixture was stirred
for 12 h. Then the mixture was diluted with water (100 mL) and
kept for 16 h at 4 °C. The precipitate was filtered off, washed
with water, and recrystallized from EtOH to give 0.46 g (64%) of

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Vatsadze et al.
Ring cleavage of salt 1d. Mixture of products 3c and 4c
(0.01 g, molar ratio 10 : 1). 1H NMR (CDCl3), δ: 0.74 (s, 0.6 H,
2 Me (4d)); 0.80—0.86 (m, 6.3 H, 2 Me (3d), CH3CH2 (4d));
0.89 (t, 3 H, CH3CH2 (3d), J = 7.3 Hz); 1.18—1.27 (m, 0.2 H,
CH2CH2Me (4d)); 1.40—1.53 (m, 2 H, CH2CH2Me (3d)); 2.00
(t, 0.2 H, NCH2CH2Me (4d), J = 7.1 Hz); 2.08—2.16 (m, 2.2 H,
NCH2CH2Me (3d), CH2 (4d)); 2.27 (dd, 2 H, CH2 (3d), J =
11.5 Hz, J = 1.8 Hz); 2.43 (d, 0.2 H, CH2 (4d), J = 11.3 Hz);
2.52 (d, 0.2 H, CH2 (4d), J = 12.7 Hz); 2.77 (d, 2 H, CH2 (3d),
J = 12.7); 2.86 (d, 0.2 H, CH2 (4d), J = 13.9 Hz); 3.03—3.17
(m, 2.1 H, CH2 (3d), H(9) (4d)); 3.23 (d, 2 H, CH2 (3d), J =
13.7 Hz).
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This work was supported by the Russian Foundation
for Basic Research (Project No. 06ꢀ03ꢀ33077).
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Received May 30, 2007