Synthesis, structure and some reactions of 4a′,5′,6′, 7′,8′,8a′-hexahydro-4′H-spiro[cyclohexane-1,9′-[1, 2,4]triazolo[5,1-b]-quinazolines]

Article abstract of DOI:10.1002/jhet.5570450527

(Chemical Equation Presented) 2′-Substituted 5′,6′, 7′,8′-tetrahydro-4′H-spiro[cyclohexane-1,9′-[1,2,4] triazolo[5,1-b]quinazolines] 3a-d were synthesized by condensation of 3-substituted 5-amino-1,2,4-triazoles 1a-d with 2-cyclohexylidene cyclohexanone 2

Full text of DOI:10.1002/jhet.5570450527

Sep-Oct 2008
1419
Synthesis, Structure and Some Reactions of 4a',5',6',7',8',8a'-
Hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazolines]
Victor M. Chernyshev1*, Dmitry A. Khoroshkin1, Andrey N. Sokolov1,
Eugene S. Gladkov2, Svetlana V. Shishkina2, Oleg V. Shishkin2, Sergey M. Desenko2,
Vitaly A. Taranushich1
1South-Russian State Technical University, 346428 Novocherkassk, Russian Federation,
tnw@novoch.ru
2State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine, Lenin
Ave 60, Kharkiv, Ukraine, 61001, gladkov@isc.kharkov.com
Received March 18, 2008
N
N
N
N
N
N
NH
NH2
DMF
NaBH4/EtOH
N
N
R
O
R
R
+
N
H
N
H
R = H, NH2, Ph, morpholin-4-ylcarbonyl
R''
HN
Bz
Bz
Ts
Ts
N
N
N
N
N
N
N
N
N
N
N
N
N
N
R
N
N
N
N
N
N
N
N
H
H
H
Br
R'
Bz
R'' = Bz, Ts
Ph
R = H, Ph, morpholin-4-ylcarbonyl
R' = Alkyl, Acyl, SO2Aryl
2'-Substituted 5',6',7',8'-tetrahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolines] 3a-d
were synthesized by condensation of 3-substituted 5-amino-1,2,4-triazoles 1a-d with 2-cyclohexylidene
cyclohexanone 2 in DMF. The compounds 3 were hydrogenated with sodium borohydride in ethanol to
give 2'-substituted cis-4a',5',6',7',8',8a'-hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quin-
azolines] 4a-d in high yields. The reactions of alkylation, acylation and sulfonylation of the compounds 4
were studied. The structure of the synthesized compounds was determined on the basis of NMR
measurements including HSQC, HMBC, NOESY techniques and confirmed by the X-ray analysis of 6 and
11b. The described synthetic protocols provide rapid access to novel and diversely substituted
hydrogenated [1,2,4]triazolo[5,1-b]quinazolines.
J. Heterocyclic Chem., 45, 1419 (2008).
INTRODUCTION
[1,2,4]triazolo[5,1-b]quinazolines. These reactions allow
to modify substituents at the positions 2 and 9 of the
triazolo[5,1-b]quinazoline system.
Fused [1,2,4]triazoloazines containing partially hydro-
genated pyrimidine ring attract attention as pharm-
acologically active compounds and models for studying
the structural properties and synthetic possibilities of
partially hydrogenated heterocycles [1-6]. During recent
years, great interest was focused on [1,2,4]triazolo[5,1-b]-
quinazolines with different degrees of hydrogenation of
the quinazoline moiety [7-16]. In many respects it is
caused by the fact that the compounds containing
annelated 1,2,4-triazole and quinazoline rings exhibit
antihypertensive activity [14,15] and act as antagonists of
adenosine [17,18] and nociceptin receptors [2].
From a variety of synthetic methods [7-16,19-21] the
condensation of 3-substituted 5-amino-1,2,4-triazoles
with aldehydes and 1,3-cyclohexandione or alkylidene-
and arylidenecyclohexanones [8,9,12,13,20] is the most
appropriate way to synthesize partially hydrogenated
The susceptibility of the dihydropyrimidine moiety of
fused heterocycles to oxidative aromatization as well as to
hydrogenation allows to enlarge remarkably the structural
diversity of those compounds [1]. For [1,2,4]triazolo[5,1-
b]quinazolines, oxidative aromatization of 9-(aryl)-6,6-
dimethyl-5,6,7,9-tetrahydro-4H-[1,2,4]triazolo[5,1-b]-
quinazolin-8-ones [13] and of 6,8,9-triphenyl-4,7,8,9-
tetrahydro-[1,2,4]triazolo[5,1-b]quinazoline [10] was
realized. However, hydrogenation of 6,8,9-triphenyl-
4,7,8,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazoline by
sodium borohydride was unsuccessful due to
impossibility of rearrangement of this substance into
imine tautomer necessary for reduction [10]. Therefore, it
is of interest to investigate the possibility of
hydrogenation of other triazolo[5,1-b]quinazolines
containing dihydropyrimidine moiety. The present article

1420
V. M. Chernyshev, D. A. Khoroshkin, A. N. Sokolov, E. S. Gladkov, S. V. Shishkina,
O. V. Shishkin, S. M. Desenko, V. A. Taranushich
Vol 45
Scheme 1
N
1N
N
N
NH
N
N
DMF
NaBH4 - EtOH
N
9
N
N
8
R
O
+
R
+
R
R
N
4
N
H
NH2
N
3
N
N
H
5
H
1a-d
4a-d
2
3a-d
a: R = H; b: R = NH2; c: R = C6H5; d: R = morpholin-4-ylcarbonyl
(Scheme 1). The configuration of the compounds 4a-d
was confirmed unambiguously by X-ray diffraction study
of their transformation products – benzyl 6 and furoyl 11b
derivatives (Figures 1 and 2).
is devoted to the synthesis of 4a',5',6',7',8',8a'-hexahydro-
4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazol-
ines] 4 by hydrogenation of 5',6',7',8'-tetrahydro-4'H-
spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolines]
3. Special consideration is given to the structure analysis
of the compounds 4 and their reactions with electrophilic
reagents.
Scheme 2
R7
R7
R7
R6
R5
R6
R5
R6
R5
N
N
N
N
N
N
NaBH4
N
N
N
RESULTS AND DISCUSSION
R
or R
R
N
H
N
H
N
H
5',6',7',8'-Tetrahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]-
triazolo[5,1-b]quinazolines] 3a-d were obtained by
condensation of 3-substituted 5-amino-1,2,4-triazoles 1a-d
with 2-cyclohexylidene cyclohexanone 2 (Scheme 1).
lit [6]
lit [24]
The molecules of triazoloquinazolines 4a-d contain at
1
Compounds 3a,b have been described earlier [20]. The H
least three nucleophilic centers N-1, N-3 and N-4, at
which electrophilic reactions may take place.
Modification of the compounds 4 by means of alkylation,
acylation and sulfonylation reactions would allow to
increase remarkably the structural diversity of these
compounds and modify their biological activity. From this
point of view, we can assume that in these reactions the
NMR spectra of the heterocycles 3c,d exhibit the following
signals: characteristic resonances for the CH2-groups at 1.1-
2.3 ppm, singlet for NH at 9.2 ppm and signals of the
substituent at the position 2.
The application of sodium borohydride is one of the
most useful methods for hydrogenation of the
heterocycles containing azolopyrimidine fragment
[6,22-25]. As established in our study, the substances
3a-d can be easily hydrogenated with sodium borohydride
in ethanol to give 4a',5',6',7',8',8a'-hexahydro-4'H-spiro-
[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolines] 4a-d
as only one diastereoisomer with 84-90% yields (Scheme
1). This fact was confirmed by the absence of signals of
compounds
4
will behave similarly to 4,5,6,7-
tetrahydro[1,2,4]triazolo[1,5-a]pyrimidines [24]. However,
until recently only alkylation of 5,7-diphenyl-4,5,6,7-
tetrahydro[1,2,4]triazolo[1,5-a]pyrimidine by dimethyl
sulfate in the presence of KOH to give 4-methyl
derivative [24] was described. Other reactions with
electrophiles were not studied. Therefore, in this paper we
investigated the alkylation, acylation and sulfonylation of
compounds 4.
1
some extra diastereoisomers in the H NMR spectra of
crude products. In comparison with the starting materials
1
3a-d, in the H NMR spectra of the substances 4a-d the
Alkylation was studied on examples of the reaction of
compound 4a with benzylhalogenides and methylacrylate
(Scheme 3). The reaction with benzyl chloride in DMSO
in the presence of KOH led to the formation of 4-benzyl
derivative 5, whereas refluxing of 4a with benzyl bromide
in methanol in the absence of base gave a bromide of the
3-benzyl derivative 6. The position of benzyl group in the
compounds 5 and 6 was established on the basis of
heteronuclear correlation NMR measurements (HMBC
and HSQC). The HMBC spectrum of the compound 5
contains the geminal correlation peaks of the benzyl CH2
protons (4.23 ppm and 5.14 ppm) with C-3a (155 ppm)
and C-4a (48 ppm), while the correlation peak with C-2
(149 ppm) is not observed. However, in the HMBC
integral intensity of aliphatic protons at 1.3-2.2 ppm is
larger on 1H and the signal of NH is shifted to 6.4-7.1
ppm. In addition, a broad singlet for H-4a appears at 3.6-
3.8 ppm. It is of interest to note that hydrogenation of
5,6,7-trisubstituted
4,7-dihydro[1,2,4]triazolo[1,5-a]-
pyrimidines can lead to the products with either trans [6]
or cis orientation [24] of the substituents at the positions 6
and 7 of the triazolopyrimidine system (Scheme 2).
In accordance with a very low value of the constant
JH-4a,H-8a (therefore, H-4a is observed as a broad singlet in
1
the H NMR spectra), hydrogenation of the compounds
3a-d leads to cis-4a',5',6',7',8',8a'-hexahydro-4'H-spiro-
[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolines] 4a-d
as a mixture of (4aR,8aS) and (4aS,8aR) enantiomers

Sep-Oct 2008
Synthesis, structure and some reactions of new partially hydrogenated
[1,2,4]triazolo[5,1-b]quinazolines
1421
spectrum of the compound 6 the methylene protons of the
benzyl group (5.23 ppm) correlate with the carbon atoms
C-2 (140 ppm) and C-3a (146 ppm), whereas the
correlation peak with C-4a is absent. The structure of
compound 6 was additionally confirmed by X-ray
diffraction study. In the ensuing discussion of the
structure, the crystallographic numbering system will be
used (Figure 1).
Scheme 3
N
BnCl, DMSO, KOH
N
3a
2
N
4a
N
Figure 1. The molecular structure of compound 6.
Ph
5
of uncharged fragment in structure 9 [28] corresponding
to the C(1)-N(1) bond in 6 is shortened and corresponding
to the C(1)-N(2) and C(1)-N(4) bonds are equalized. This
allows one to suggest that the A and B resonance
structures introduce the main contribution in the structure
of the compound 6.
N
BnBr, MeOH
N
4a
N
N
H
Br
Ph
6
Scheme 5
Me
Cl
Me
Me
1. CH2=CHCOOMe,
MeONa, MeOH
2. NaOH, H2O
N
N
N
N
N
N
N
N
N
Me
ClO4
Me
Ph
N
Ph
N
H
N
N
N
N
H
N
N
N
3. H+
Cl
Cl
Me
NH2
NHMe
7
8
9
COOH
10
The bromide anion and the organic cation are bonded
by the N(1)-H(1N)…Br(1) intermolecular hydrogen bond
(H…Br 2.40 Å, N-H…Br 170°). The tetrahydro-
pyrimidine ring of organic cation adopts the asymmetric
half-chair conformation. Deviations of the C(4) and C(9)
atoms from the mean plane of the remaining atoms of the
ring are 0.55 Å and -0.17 Å, respectively. The fused
cyclohexane and tetrahydropyrimidine rings have cis-
junction (the H(4)-C(4)-C(9)-H(9) torsion angle is 55º).
Both cyclohexane rings adopt the chair conformation.
The interaction of 4a with methylacrylate in the
absence of strong base was unsuccessful under various
experimental conditions. However, refluxing of 4a with
excess of methylacrylate in methanol in the presence of
MeONa and subsequent one-pot hydrolysis of the
resultant ester allowed to obtain acid 10 in 77% yield. The
position of the carboxyethyl group was established by
HMBC and HSQC experiments. The HMBC spectrum of
compound 10 contains correlation peaks of NCH2 protons
(3.32 ppm and 3.96 ppm) with C-3a (153.4 ppm) and
C-4a (47.4 ppm), whereas the correlation peaks of these
protons with C-2 (148.1 ppm) are not observed.
In accordance with the X-ray diffraction data
compound 6 exists as a salt formed by bromide anion and
organic cation (Figure 1). The position of the hydrogen
atom at the N(1) atom is established unambiguously from
the electron density difference map. This allows one to
assume that the structure of the organic cation may be
described as a superposition of three resonance structures
(Scheme 4).
Scheme 4
N
N
N
N
N
N
N
C
N
R
N
N
H
N
H
N
H
R
R
A
B
It should be noted that the C(1)-N(2) bond (1.356(3) Å)
in the compound 6 is longer as compared with the
C(1)-N(4) and C(1)-N(1) bonds which are equalized
(1.331(3) Å and 1.326(3) Å, respectively). Such a
redistribution of the electron density was observed in the
similar fragments with the positively charged N(1) atom
in the structures 7 [26] and 8 [27] (Scheme 5). In the case
The obtained results show that compounds 4 bear
resemblance to 1-substituted 5-amino-1,2,4-triazoles in

1422
V. M. Chernyshev, D. A. Khoroshkin, A. N. Sokolov, E. S. Gladkov, S. V. Shishkina,
O. V. Shishkin, S. M. Desenko, V. A. Taranushich
Vol 45
alkylation. In the presence of strong bases, 1-substituted 5-
amino-1,2,4-triazoles are alkylated at the exocyclic amino
group (position 4 of the triazoloquinazoline system 4). In
this case, the deprotonation of amino group precedes the
attack of electrophile [29]. Alkylation of 1-substituted 5-
amino-1,2,4-triazoles in neutral media occurs at the atom
with the highest electronic density, e.g. N-4 of the triazole
ring (the position 3 of the system 4) [30,31].
The tetrahydropyrimidine ring of the compound 11b
adopts the half-chair conformation. The tetrahydro-
pyrimidine and C(4)…C(9) cyclohexane ring have cis-
junction (the H(4)-C(4)-C(9)-H(9) torsion angles is –61º).
Morpholine and both cyclohexane rings of the compound
11b adopt the chair conformation. The carbonyl group of
the substituent at the N(4) atom is turned noticeably
relatively the C(1)-N(4) bond (the C(1)-N(4)-C(10)-O(1)
torsion angle is 137.2(2)º) and is non-coplanar to the
plane of the furane ring (the O(1)-C(10)-C(11)-C(12)
torsion angle is –22.6(3)º). The carbonyl group of the
substituent at the C(2) atom is non-coplanar to the triazole
ring (the N(2)-C(2)-C(20)-O(3) torsion angle is 22.1(2)º).
The nitrogen atom of the morpholine ring has a slightly
pyramidal configuration (the sum of the bond angles
centered on the N(5) atom is 357.7°).
Acylation of compounds 4c and 4d resulted in the
formation of 4-acyl derivatives 11a,b (Scheme 6). The 1H
NMR spectra of compounds 11a,b show no signals for
H-4, and the signal of H-4a is shifted downfield by 0.64
ppm in comparison with the starting material 4c,d. This
fact indicates that the acyl group is bonded to the N-4
atom rather than to the N-1 or N-3. The position of the
acyl group in the substance 11a was also confirmed by 13
C
NMR. The chemical shift of C-2 (157.9 ppm) in the 13C
NMR spectrum was almost the same in comparison with
that in the spectrum of the starting substance 4c (157.4
ppm), whereas the signal of C-3a was shifted upfield by 4
ppm apparently owing to the effect of magnetic
anisotropy of the acetyl group.
All attempts of sulfonylation of 4a with sulfonyl-
chlorides in boiling pyridine were unsuccessful, only the
starting compounds were isolated from the reaction
mixtures. The sulfonyl derivatives 12a,b were synthesized
in 40% yield trough sulfonylation of the sodium salt of
the compound 4a obtained in situ by the action of NaH
(Scheme 7). The direction of sulfonylation was
1
determined by the H and 13C NMR spectra. Similarly to
Scheme 6
1
the acyl derivatives 11a,b, in the H NMR spectra of
12a,b the signal of H-4 is absent, and moreover, the signal
of H-4a is shifted downfield by about 0.8 ppm in
comparison with the starting substance 4a. In the 13C
NMR spectrum of 12b the signal of C-2 is almost
invariable, whereas the signal of C-3a is shifted upfield
6.3 ppm in comparison with the spectrum of starting
compound 4a due to magnetic anisotropy of the sulfonyl
group. Furthermore, the signal of the o-protons of the
tosyl group (7.93 ppm) gives the cross-peaks with the
signals of H-4a (4.50 ppm) and CH2 protons (0.74 ppm
and 2.46 ppm) in the NOESY spectrum of 12b. This
finding unambiguously confirmed the fact that the N-4
sulfonyl derivative was obtained.
N
(i) or (ii)
N
O
R
4c,d
N
N
R'
11a,b
11a: R = C6H5, R' = Me;
11b: R = morpholin-4-ylcarbonyl, R' = 2-
furyl
Reagents and conditions: (i) Ac2O, refluxing for 2.5 h;
(ii) furoyl chloride / Py, refluxing for 15 min
The direction of the acylation was unequivocally
confirmed by X-ray diffraction study of the compound
11b (Figure 2).
Scheme 7
N
N
N
N
NaH, DMF
ArSO2Cl
N
N
4a
N
S
N
O
O
Na
Ar
a: Ar = C6H5; b: R = p-CH3C6H4
12a,b
Compound 4b contains reactive amino group at position
2, therefore its behavior in the acylation reactions is very
special. The benzoylation of 4b with equimolar amount of
benzoyl chloride under mild conditions led to the
formation of monobenzoyl derivative 13, whereas
Figure 2. The molecular structure of compound 11b.

Sep-Oct 2008
Synthesis, structure and some reactions of new partially hydrogenated
[1,2,4]triazolo[5,1-b]quinazolines
1423
refluxing in pyridine with excess of benzoyl chloride gave
the tribenzoyl derivative 14 (Scheme 8). In the H NMR
1-substitured 5-amino-1,2,4-triazoles [32], whereas the
compound 4b is analogous to 1-substitured 3,5-diamino-
1,2,4-triazoles [33-35].
1
spectrum of 13 the signal of the amino group disappears,
and a broad singlet of amide proton at 10.27 ppm appears.
The singlet of H-4 is conserved and shifted downfield of
about 0.5 ppm, the position of the H-4a signal is almost
invariable (in comparison with 4b). In the spectrum of the
tribenzoyl derivative 14 the signals of NH are absent; the
chemical shift of H-4a (4.45 ppm) is characteristic of the
4-acyl derivatives. In comparison with the starting
compound 4b, in the 13C NMR spectrum of 14, the carbon
signals of the triazole ring are shifted upfield due to
magnetic anisotropy of the carbonyl groups. Complete
CONCLUSION
Hydrogenation of 5',6',7',8'-tetrahydro-4'H-spiro[cyclo-
hexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolines] 3a-d in
ethanol leads to the formation of cis-4a',5',6',7',8',8a'-
hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-
b]quinazolines] 4a-d in a good yield. The structure of cis-
4a',5',6',7',8',8a'-hexahydro-4'H-spiro[cyclohexane-1,9'-
[1,2,4]triazolo[5,1-b]quinazolines] can be easily modified
by alkylation, acylation and sulfonylation reactions in
which the compounds 4a,c,d behave analogously to
1-substituted 5-amino-1,2,4-triazoles, and compound 4b
is similar to 1-substituted 3,5-diamino-1,2,4-triazoles. The
high susceptibility of the compounds 4 to function-
alization opens up the possibility for their use in
combinatorial synthesis.
1
similarity of the signals of two benzoyl groups in the H
and 13C NMR spectra confirms the structure of 14 and
excludes alternative structures of N-1 and N-3 isomers.
Short-time refluxing of 4b with an equimolar amount or
a small excess of tosyl chloride in pyridine led to the
formation of sulfamide 15, whereas long-time refluxing
with an excess of tosyl chloride gave the disulfonyl
1
derivative 16 (Scheme 8). The H NMR spectrum of the
EXPERIMENTAL
substance 15 contains a broad singlet of sulfamide proton
at 10.45 ppm, the singlet of H-4 is shifted downfield of
about 0.5 ppm, and the chemical shift of H-4a is not
Melting points were determined in open capillary tubes in a
1
Thiele apparatus and are uncorrected. H- and 13C NMR spectra
Scheme 8
O
PhCOCl (1 eq)
TsCl (1 eq)
Py, reflux
Ph
Ts
HN
N
N
N
N
N
N
HN
MeCN-Py, 0-5oC
N
H
N
H
13
15
4b
Ph
O
PhCOCl (excess)
Py, reflux
N
N
TsCl (excess)
Py, reflux
N
Ts
Ts
N
N
N
N
O
N
Ph
N
N
H
Ph
O
14
16
changed (in comparison with 4b). In the 1H NMR
spectrum of 16 the NH signals of amino and sulfamide
groups are absent, the singlet of H-4 (7.31 ppm) is
downfield shifted in comparison with the starting
compound 4b (6.37 ppm), whereas the position of H-4a
signal is almost unchanged. The signal of C-2 (148.5
ppm) in the 13C NMR spectrum is shifted upfield by 11.7
ppm in comparison with 4b (160.2 ppm), whereas the
signal of C-3a is shifted downfield only by 1.4 ppm.
Complete similarity of the signals of both tosyl groups in
were recorded on a Bruker DRX500 instrument at 500 MHz and
125 MHz respectively and Bruker AM300 instrument at 300
MHz (75 MHz for 13C) in DMSO-d6 as solvent and TMS as
internal standard. Mass spectra were recorded in the form of m/z
(intensity relative to base 100) on a Finnigan MAT Incos 50 at
70 eV. Elemental analyses were determined using a Perkin-
Elmer 2400 instrument.
2-Cyclohexylidene cyclohexanone 2 [36] and 5-amino-3-
(morpholin-4-ylcarbonyl)-1,2,4-triazole 1d [37] were obtained
by known methods. All other chemicals are commercially
available.
General Procedure for the preparation of 5',6',7',8'-
tetrahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazolines] 3a-d. A mixture of triazole 1a-d (5 mmol) and the
compound 2 (5 mmol) was refluxed in DMF (0.8 mL) for 2
hours, diluted with ethanol (4 mL) and cooled to room
1
the H and 13C NMR spectra confirms unambiguously the
structure of the compound 16.
On the whole, the obtained results show, that in the
acylation reactions the compounds 4c,d are similar to

1424
V. M. Chernyshev, D. A. Khoroshkin, A. N. Sokolov, E. S. Gladkov, S. V. Shishkina,
O. V. Shishkin, S. M. Desenko, V. A. Taranushich
Vol 45
temperature. The precipitate that formed was collected by
filtration and recrystallized.
2'-Phenyl-4a',5',6',7',8',8a'-hexahydro-4'H-spiro[cyclo-
hexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (4c). This
compound was obtained in 90% yield as white crystals
5',6',7',8'-Tetrahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]-
triazolo[5,1-b]quinazoline] (3a). This compound was
obtained in 56% yield as white crystals (ethanol), mp 234-235°,
lit [20] mp 233-234°. Spectral data for compound 3a were in
agreement with those, reported in the literature [20].
2'-Amino-5',6',7',8'-tetrahydro-4'H-spiro[cyclohexane-
1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (3b). This compound
was obtained in 82% yield as white crystals (DMF-ethanol), mp
264-265°, lit [20] mp 251°. Spectral data for compound 3b were
in agreement with those, reported in the literature [20].
1
(ethanol), mp 176-177°; H NMR: ꢀ 0.97-2.23 (m, 19H), 3.80
(br s, 1H, H-4a), 7.01 (br s, 1H, NH), 7.25-7.37 (m, 3H, phenyl),
7.87 (m, 2H, phenyl); 13C NMR: ꢀ 19.60, 20.75, 22.03, 22.24,
25.35, 25.60, 30.26, 32.08, 36.03, 37.58, 45.39 (C-4a), 60.18 (C-
9), 125.69, 128.61, 128.80, 132.74, 154.02 (C-3a), 157.35 (C-2);
MS: m/z 322 (M+, 29), 161 (28), 146 (100), 104 (57), 91 (19), 81
(38), 77 (47), 41 (92). Anal. Calcd. for C20H26N4: C, 74.50; H,
8.13; N, 17.37. Found: C, 74.69; H, 8.17; N, 17.14.
2'-(Morpholin-4-ylcarbonyl)-4a',5',6',7',8',8a'-hexahy-
dro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazo-
line] (4d). This compound was obtained in 84% yield as white
crystals (ethanol), mp 198-199°; 1H NMR: ꢀ 0.89 (m, 1H), 1.29-
2.11 (m, 18H), 3.57-3.78 (m, 9H, H-4a and morpholine), 7.09
(br s, 1H, NH); 13C NMR: ꢀ 19.54, 20.71, 21.92, 22.12, 25.25,
25.48, 30.06, 31.96, 35.87, 37.61, 42.50 (NCH2), 45.39 (C-4a),
47.38 (NCH2), 60.57 (C-9), 66.58 (OCH2), 66.94 (OCH2),
153.13 (C-3a), 161.49 (C-2), 174.04 (C=O); MS: m/z 359 (M+,
14), 246 (28), 203 (18), 191 (10), 81 (42), 41 (100). Anal. Calcd.
for C19H29N5O2: C, 63.48; H, 8.13; N, 19.48. Found: C, 63.56; H,
8.18; N, 19.27.
2'-Phenyl-5',6',7',8'-tetrahydro-4'H-spiro[cyclohexane-
1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (3c). This compound
was obtained in 60% yield as white crystals (DMF-ethanol), mp
1
194-196°; H NMR: ꢀ 1.21-1.30 (m, 1H), 1.58-1.89 (m, 11H),
2.05-2.30 (m, 6H), 7.32-7.51 (m, 3H, phenyl), 7.88-8.02 (m, 2H,
phenyl), 9.20 (s, 1H, NH); 13C NMR: ꢀ 22.09, 22.82, 23.47,
23.88, 25.19, 26.55, 34.76, 61.46, 106.85, 125.77, 128.72,
128.95, 132.35, 150.12 (C-3a), 157.23 (C-2) ; MS: m/z 320 (M+,
56), 291 (21), 277 (100), 264 (23), 217 (23), 174 (42), 160 (13).
Anal. Calcd. for C20H24N4: C, 74.97; H, 7.55; N, 17.48. Found:
C, 75.14; H, 7.61; N, 17.26.
4'-Benzyl-4a',5',6',7',8',8a'-hexahydro-4'H-spiro[cyclo-
hexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (5). Finely
ground KOH (0.77 g, 13.75 mmol) was added to a solution of
compound 4a (1.70 g, 6.91 mmol) in DMSO (8.5 mL) and the
resultant mixture was stirred at room temperature within 10
minutes. Then benzylchloride (1.14 g, 9.0 mmol) was added
slowly and the reaction mixture was stirred at room temperature
for 3 h. The reaction mixture was then poured onto 40 mL of
water. The formed precipitate was collected by filtration and
recrystallized from ethanol to give 1.64 g (72%) of 5, mp 155-
2'-(Morpholin-4-ylcarbonyl)-5',6',7',8'-tetrahydro-4'H-
spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline]
(3d). This compound was obtained in 58% yield as white
1
crystals (ethanol), mp 186-188°; H NMR: ꢀ 1.13-1.29 (m, 1H),
1.49-1.88 (m, 11H), 1.95-2.08 (m, 6H), 3.56-3.69 (m, 8H,
morpholine), 9.25 (s, 1H, NH); MS: m/z 357 (M+, 16), 314 (21),
243 (100), 217 (92), 201 (43), 187 (41). Anal. Calcd. for
C19H27N5O2: C, 63.84; H, 7.61; N, 19.59. Found: C, 63.79; H,
7.64; N, 19.72.
General Procedure for the preparation of 4a',5',6',7',
8',8a'-hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo-
[5,1-b]quinazolines] 4a-d. To a stirred suspension of compound
3a-d (4 mmol) in ethanol (10 mL) sodium borohydride (0.23 g,
6 mmol) was subsequently added in small portions at 50-60°
within 20 minutes. After the addition was complete, the reaction
mixture was evaporated to small volume and diluted with water
(10 mL). The formed precipitate was collected by filtration,
washed with water and recrystallized.
1
157°; H NMR: ꢀ 0.90 (m, 1H), 1.21-1.79 (m, 15H), 2.08-2.23
(m, 3H), 3.47 (br s, 1H, H-4a), 4.23, 5.14 (2d, each 1H, CH2 of
benzyl, J = 15.8 Hz) 7.17-7.32 (m, 5H, phenyl), 7.45 (s, 1H, H-
2); 13C NMR: ꢀ 19.65, 21.16, 21.62, 21.96, 25.26, 25.41, 27.43,
31.79, 37.11, 37.97, 47.98 (C-4a), 48.65 (CH2 of benzyl), 59.49
(C-9), 127.62, 127.88, 128.90, 138.01, 148.52 (C-2), 154.98 (C-
3a); Anal. Calcd. for C21H28N4: C, 74.96; H, 8.39; N, 16.65.
Found: C, 74.74; H, 8.42; N, 16.84.
3'-Benzyl-4a',5',6',7',8',8a'-hexahydro-3'H-spiro[cyclo-
hexane-1,9'-[1,2,4]triazolo[5,1-b]quinazolinium] bromide (6).
A mixture of compound 4a (0.5 g, 2.03 mmol), benzyl bromide
(0.45 g, 2.64 mmol) and methanol (3 mL) was refluxed for 4 h
and cooled to ambient temperature. After standing overnight the
crystals that precipitated were collected by filtration and
recrystallized from ethanol to give 0.7 g (82%) of 6, mp 230-
4a',5',6',7',8',8a'-Hexahydro-4'H-spiro[cyclohexane-1,9'-
[1,2,4]triazolo[5,1-b]quinazoline] (4a). This compound was
obtained in 85% yield as white crystals (ethanol), mp 220-222°;
1H NMR: ꢀ 0.88 (m, 1H), 1.18-1.88 (m, 16H), 2.00-2.15 (m,
2H), 3.73 (br s, 1H, H-4a), 6.81 (br s, 1H, NH), 7.29 (s, 1H, H-
2); 13C NMR: ꢀ 19.58, 20.70, 22.00, 22.21, 25.34, 25.60, 30.22,
32.05, 36.07, 37.63, 45.45 (C-4a), 59.86 (C-9), 148.41 (C-2),
153.15 (C-3a); MS: m/z 246 (M+, 16), 217 (13), 203 (20), 191
(22), 162 (23), 137 (28), 123 (22), 97 (18), 85 (36), 41 (100).
Anal. Calcd. for C14H22N4: C, 68.26; H, 9.00; N, 22.74. Found:
C, 68.21; H, 9.12; N, 22.49.
2'-Amino-4a',5',6',7',8',8a'-hexahydro-4'H-spiro[cyclohex-
ane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (4b). This com-
pound was obtained in 87% yield as white crystals (DMF-
ethanol), mp 291-293°; 1H NMR: ꢀ 0.93-2.01 (m, 19H), 3.64 (br
s, 1H, H-4a), 4.68 (br s, 2H, NH2), 6.37 (br s, 1H, NH); 13C
NMR: ꢀ 19.22, 20.36, 21.65, 21.95, 25.04, 25.33, 29.97, 31.64,
35.64, 36.67, 44.95 (C-4a), 58.33 (C-9), 151.84 (C-3a), 160.20
(C-2); MS: m/z 261 (M+, 100), 232 (26), 218 (40), 206 (15), 190
(21), 176 (17), 162 (42), 99 (99). Anal. Calcd. for C14H23N5: C,
64.34; H, 8.87; N, 26.79. Found: C, 64.00; H, 9.00; N, 27.01.
1
232; H NMR: ꢀ 0.69 (m, 1H), 1.21-1.79 (m, 14H), 1.93-2.11
(m, 3H), 2.33 (d, 1H, J = 12.9), 4.00 (br, 1H, H-4a), 5.20, 5.28
(2d, each 1H, CH2 of benzyl, J = 15.8 Hz), 7.13-7.46 (m, 5H,
phenyl), 8.60 (s, 1H, H-2), 9.07 (br s, 1H, NH); 13C NMR: ꢀ
19.41, 20.57, 21.56, 21.67, 24.86, 24.91, 28.88, 30.87, 34.77,
36.83, 46.60 (C-4a), 47.43 (CH2 of benzyl), 62.94 (C-9), 128.16,
128.97, 129.45, 134.69, 140.01 (C-2), 146.26 (C-3a); Anal.
Calcd. for C21H29N4Br: C, 60.43; H, 7.00; N, 19.14. Found: C,
60.14; H, 7.22; N, 18.89.
3-(4a',5',6',7',8',8a'-Hexahydro-4'H-spiro[cyclohexane-1,9'-
[1,2,4]triazolo[5,1-b]quinazolin]-4'-yl)propanoic acid (10).
Compound 4a (0.5 g, 2.03 mmol) and methylacrylate (0.96 g,
11.03 mmol) were added to a solution of sodium (0.09 g, 3.91
mmol) in methanol (3 mL). The resulted mixture was refluxed

Sep-Oct 2008
Synthesis, structure and some reactions of new partially hydrogenated
[1,2,4]triazolo[5,1-b]quinazolines
1425
for 8 hours, then diluted with solution of NaOH (0.44 g, 11
mmol) in water (2 mL) and additionally refluxed for 30 minutes.
The solution was cooled, diluted with water (30 mL) and
extracted with chloroform (10 mL). The water layer was
acidified by acetic acid. The resultant solid was collected by
filtration, washed with water and crystallized from ethanol to
give 0.5 g (77%) of 10, mp 228-229°; 1H NMR: ꢀ 0.81-1.80 (m,
16H), 2.06-2.36 (m, 4H), 2.55 (m, 1H), 3.32 (m, 1H), 3.71 (br s,
1H, H-4a), 3.96 (m, 1H,) 7.39 (s, 1H, H-2), 12.25 (br s, 1H,
OH); 13C NMR: ꢀ 19.17, 20.54, 21.31, 21.68, 24.87, 25.08,
27.16, 30.79 (C-2 of propanoic acid), 31.46, 36.94, 37.21, 40.14
(C-3 of propanoic acid), 47.38 (C-4a), 59.05 (C-9), 148.06 (C-
2), 153.41 (C-3a), 173.16 (C=O); MS: m/z 318 (M+, 40), 273
(12), 259 (18), 245 (22), 41 (100). Anal. Calcd. for C17H26N4O2:
C, 64.13; H, 8.23; N, 17.60. Found: C, 64.22; H, 8.28; N, 17.77.
4'-Acetyl-2'-phenyl-4a',5',6',7',8',8a'-hexahydro-4'H-spiro-
[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (11a). A
mixture of compound 4c (1 g, 3.10 mmol) and acetic anhydride
(4 mL) was refluxed for 2 hours, diluted with 10 mL of water
and cooled to room temperature. The precipitate that formed was
collected by filtration and recrystallized from ethanol to give
4'-[(4-Methylphenyl)sulfonyl]-4a',5',6',7',8',8a'-hexahydro-
4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline]
(12b). This compound was prepared analogously to compound
1
12a. Yield 0.32 g (40%), mp 188-189°; H NMR: ꢀ ꢁ0.17 (m,
1H), 0.74 (q, 1H, J = 13.0), 1.09-1.69 (m, 13H), 1.90 (br, 1H),
2.05 (m, 1H), 2.38 (s, 3H, CH3), 2.46 (m, 2H), 4.50 (br s, 1H, H-
4a), 7.43 (d, 2H, J = 8.2, aromat.), 7.74 (s, 1H, H-2), 7.93 (d, 2H,
J = 8.2, aromat.); 13C NMR: ꢀ 19.00, 20.82, 21.10, 21.27, 21.33,
23.92, 24.68, 29.23, 30.92, 34.09, 42.02, 53.66, 60.75 (C-9),
127.46, 129.70, 136.68, 144.41, 146.88 (C-3a), 148.61 (C-2);
MS: m/z 400 (M+, 2), 336 (57), 293 (15), 254 (22), 245 (35), 175
(19), 155 (38), 91 (100). Anal. Calcd. for C21H28N4O2S: C,
62.97; H, 7.05; N, 13.99. Found: C, 62.69; H, 6.98; N, 14.16.
2'-(Benzoylamino)-4a',5',6',7',8',8a'-hexahydro-4'H-spiro-
[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (13).
A
cold (0°) solution of benzoyl chloride (0.27 g, 1.9 mmol)
dissolved in 1 mL of dry acetonitrile was added drop by drop to
a magnetically stirred mixture of compound 4b (0.5 g, 1.9
mmol), dry acetonitrile (2 mL) and pyridine (0.5 g, 6 mmol) at
0-5 °C. After the addition was complete, the solution was stirred
for 30 minutes and then diluted with water (10 mL). The
resultant solid was collected by filtration, washed with water and
crystallized from ethanol to give 0.42 g (61%) of 13, mp 142-
1
1.02 g (90%) of 11a, mp 143-144°; H NMR: ꢀ ꢁ0.11 (m, 1H),
0.85-0.96 (m, 1H), 1.13-1.24 (m, 1H), 1.38-1.83 (m, 12H), 2.00
(br, 1H), 2.20-2.29 (m, 1H), 2.48 (m, 4H, CH3 and CH), 3.31
(br, 1H), 4.44 (br s, 1H, H-4a), 7.40-7.47 (m, 3H, phenyl), 7.96-
7.98 (m, 2H, phenyl); 13C NMR: ꢀ 20.39, 21.86, 22.03, 22.08,
24.56, 24.90, 25.24, 28.49, 31.24, 34.00, 41.27, 51.22 (C-4a),
62.29 (C-9), 125.95, 129.14, 129.52, 131.42, 149.97 (C-3a),
157.87 (C-2), 170.30 (C=O); MS: m/z 364 (M+, 1), 43 (100), 41
(19). Anal. Calcd. for C22H28N4O: C, 72.50; H, 7.74; N, 15.37.
Found: C, 72.71; H, 7.69; N, 15.21.
4'-(2-Furoyl)-2'-(morpholin-4-ylcarbonyl)-4a',5',6',7',8',
8a'-hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazoline] (11b). A mixture of compound 4d (1 g, 2.78 mmol),
pyridine (2 mL) and furoyl chloride (0.55 g, 4.18 mmol) was
refluxed for 15 minutes, diluted with 3 mL of ethanol and cooled
to room temperature. The precipitate that formed was collected by
filtration and recrystallized from ethanol to give 0.81 g (64%) of
11b, mp 180-183°; 1H NMR: ꢀ 0.98-1.97 (m, 16H), 2.17 (m, 1H),
2.69 (m, 1H), 3.31 (br, 1H), 3.41-3.55 (m, 8H, morpholine), 4.39
(br s, 1H, H-4a), 6.68 (br, 1H, furan), 7.26 (m, 1H, furan), 7.87
(br, 1H, furan); Anal. Calcd. for C24H31N5O4: C, 63.56; H, 6.89; N,
15.44. Found: C, 63.51; H, 6.94; N, 15.19.
4'-(Phenylsulfonyl)-4a',5',6',7',8',8a'-hexahydro-4'H-spiro-
[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]quinazoline] (12a).
Sodium hydride (0.2 g, 5 mmol, 60% dispersion in mineral oil)
was added carefully to a solution of compound 4a (0.5 g, 2.03
mmol) in dry dimethylformamide (3 mL). The mixture was
magnetically stirred at 50-60 °C for 30 minutes and cooled to -5
°C. The solution of benzenesulfonyl chloride (0.708 g, 4.0
mmol) in dry dimethylformamide (2 mL) was added drop by
drop within 5 minutes and resulted mixture was additionally
stirred for 20 minutes then poured onto water (20 mL). The
precipitate was collected by filtration, washed thoroughly with
water, cold (0°) ethanol and crystallized from chloroform-
ethanol (1:3) mixture to give 0.31 g (40%) of 12a, mp 173-175°;
1H NMR: ꢀ ꢁ0.18 (m, 1H), 0.83-1.68 (m, 15H), 1.88 (br, 1H),
2.04 (m, 1H), 1.20 (m, 1H), 4.49 (br s, 1H, H-4a), 7.58-7.77 (m,
4H, 3H of phenyl and H-2), 8.06 (m, 2H, phenyl); MS: m/z 386
(M+, 12), 322 (68), 295 (15), 279 (20), 245 (84), 240 (30), 225
(10), 141 (18), 77 (100), 41 (59). Anal. Calcd. for C20H26N4O2S:
C, 62.15; H, 6.78; N, 14.50. Found: C, 62.21; H, 6.78; N, 14.73.
1
144°; H NMR: ꢀ 1.00 (m, 1H), 1.27-2.07 (m, 18H), 3.78 (br s,
1H, H-4a), 6.90 (br s, 1H, NH), 7.44-7.55 (m, 3H, phenyl), 7.90
(m, 2H, phenyl), 10.27 (br s, 1H, CONH); MS: m/z 365 (M+,
31), 322 (16), 310 (10), 204 (31), 189 (34), 105 (100), 77 (85).
Anal. Calcd. for C21H27N5O: C, 69.01; H, 7.45; N, 19.16. Found:
C, 69.20; H, 7.58; N, 18.90.
4'-Benzoyl-2'-(N-benzoylbenzamido)-4a',5',6',7',8',8a'-
hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazoline] (14). A mixture of compound 4b (0.5 g, 1.9 mmol),
pyridine (3 mL) and benzoyl chloride (0.93 g, 6.6 mmol) was
refluxed for 1 hour then water (10 mL) was added. The resultant
solid was collected by filtration and recrystallized from ethanol to
give white crystals (0.71 g, 65%) of 14, mp 189-190°; 1H
NMR: ꢀ 0.16 (m, 1H), 0.88 (m, 1H), 1.23-1.94 (m, 14H), 2.42 (m,
2H), 2.62 (m, 1H), 4.45 (d, 1H, H-4a, J = 2.9 Hz), 7.33-7.57 (m,
15H, phenyl protons); 13C NMR: ꢀ 19.65, 21.01, 21.16, 21.50,
24.30, 24.55, 27.67, 30.90, 34.39, 39.09, 51.48 (C-4a), 62.11 (C-
9), 128.1, 128.37, 128.64, 128.69, 131.60, 132.84, 133.33, 135.13,
149.50, 153.30 (C-2, C-3a), 169.58 (C=O), 171.06 (2C=O); MS:
m/z 400 (M+, 2), 336 (57), 293 (15), 254 (22), 245 (35), 175 (19),
155 (38), 91 (100). Anal. Calcd. for C35H35N5O3: C, 73.28; H,
6.15; N, 12.21. Found: C, 73.22; H, 6.08; N, 12.46.
2'-([(4-Methylphenyl)sulfonyl]amino)-4a',5',6',7',8',8a'-
hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazoline] (15). A mixture of compound 4b (0.5 g, 1.9
mmol), pyridine (3mL) and tosyl chloride (0.43 g, 2.28 mmol)
was refluxed for 10 minutes, then water (10 mL) was added. The
resultant solid was collected by filtration and recrystallized from
DMF-ethanol mixture (1:3) to give white crystals (0.55 g, 70%)
1
of 15, mp 232-234°; H NMR: ꢀ 0.83 (m, 1H), 1.23-1.98 (m,
18H), 2.35 (s, 3H, CH3), 3.66 (br s, 1H, H-4a), 6.86 (br s, 1H,
NH), 7.33 (d, 2H, J = 8.2, aromat.), 7.74 (d, 2H, J = 8.2,
aromat.), 10.45 (br s, 1H, SO2NH); m/z 415 (M+, 36), 306 (11),
260 (46), 254 (21), 245 (28), 239 (25), 218 (16), 107 (38), 91
(100). Anal. Calcd. for C21H29N5O2S: C, 60.70; H, 7.03; N,
16.85. Found: C, 60.95; H, 7.18; N, 16.53.
2'-(bis[(4-Methylphenyl)sulfonyl]amino)-4a',5',6',7',8',8a'-
hexahydro-4'H-spiro[cyclohexane-1,9'-[1,2,4]triazolo[5,1-b]-
quinazoline] (16). A mixture of compound 4b (0.5 g, 1.9

1426
V. M. Chernyshev, D. A. Khoroshkin, A. N. Sokolov, E. S. Gladkov, S. V. Shishkina,
O. V. Shishkin, S. M. Desenko, V. A. Taranushich
Vol 45
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mmol), pyridine (3mL) and tosyl chloride (0.9 g, 4.8 mmol) was
refluxed for 1 hour, then water (10 mL) was added. The resultant
solid was collected by filtration and recrystallized from DMF-
ethanol mixture (1:3) to give white crystals (0.76 g, 70%) of 16,
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[18] Turner, C. P.; Blackburn, M. R.; Rivkees, S. A. J. Mol.
Endocrinol. 2004, 32, 129.
[19] Lee, K.-J.; Kim, S. H.; Kim, S.; Park, H; Cho, Y. R.;
Chung, B. Y.; Schweizer, E. E. Synthesis 1994, 1057.
[20] Desenko, S. M.; Orlov, V. D.; Éstrada Kh. Chem.
Heterocycl. Compd. (Engl. Transl.) 1990, 26, 839; Khim.
Geterotsikl. Soedin. 1990, 26, 999.
[21] Berecz, G.; Reiter, J.; Csaszar, J. J. Heterocycl. Chem.
1999, 36, 1199.
[22] Dalinger, I. L.; Vatsadse, I. A.; Shevelev, S. A.;
Ivachtchenko, A. V. J. Comb. Chem. 2005, 7, 236.
[23] Bellec, C.; Lhommet, G. J. Heterocycl. Chem. 1995, 32,
1793.
[24] Desenko, S. M.; Orlov, V. D.; Lipson, V. V.; Shishkin, O.
V.; Lindeman, S. V.; Struchkov, Y. T. Chem. Heterocycl. Compd.
(Engl. Transl.) 1994, 30, 851; Khim. Geterotsikl. Soedin. 1994, 30,
981.
[25] Desenko, S. M.; Orlov, V. D.; Lipson, V. V. Chem.
Heterocycl. Compd. (Engl. Transl.) 1990, 26, 1362; Khim.
Geterotsikl. Soedin. 1990, 26, 1638.
1
mp 246-248°; H NMR: ꢀ 0.83 (m, 1H), 1.25-2.05 (m, 18H),
2.43 (s, 6H, 2CH3), 3.80 (br s, 1H, H-4a), 7.31 (br s, 1H, NH),
7.44 (d, 4H, J = 8.2, aromat.), 7.84 (d, 4H, J = 8.2, aromat.); 13
C
NMR: ꢀ 19.09, 20.25, 21.20 (2CH3), 21.46, 21.54, 24.83, 24.89,
29.56, 31.51, 36.15, 37.26, 44.73 (C-4a), 60.08 (C-9), 128.26,
129.53, 136.44, 145.15, 148.51 (C-2), 153.27 (C-3a); MS: m/z
569 (M+, 2), 414 (20), 155 (25), 91 (100). Anal. Calcd. for
C28H35N5O4S2: C, 59.03; H, 6.19; N, 12.29. Found: C, 58.96; H,
6.08; N, 12.47.
X-ray diffraction study. The colorless crystals of
6
(C21H29N4Br) are monoclinic. At 293 K a = 9.628(4), b =
9.605(2), c = 11.077(2) Å, ꢁ = 100.19(2)º, V = 1008.2(5) Å3, Mr
= 417.39, Z = 2, space group P21, dcalc= 1.375 g/cm3, μ(MoKꢂ) =
2.051 mm-1, F(000) = 436. Intensities of 8472 reflections (4611
independent, Rint = 0.021) were measured on the «Xcalibur-3»
diffractometer (graphite monochromated MoKꢂ radiation, CCD
detector, ꢃ-scaning, 2ꢄmax = 60°). The structure was solved by
direct method using SHELXTL package [38]. The absorption
correction was carried out using multi-scan method (Tmin=0.685,
Tmax=0.821). Position of the hydrogen atoms were located from
electron density difference maps and refined in isotropic
approximation. Absolute configuration of chiral centres was
established based on Flack parameter 0.009(7). Full-matrix
least-squares refinement against F2 in anisotropic approximation
using 4594 reflections was converged to wR2 = 0.067 (R1
=
0.031 for 3144 reflections with F>4ꢀ(F), S = 0.860. The final
atomic coordinates, and crystallographic data for molecule 6
have been deposited to the Cambridge Crystallographic Data
Centre, 12 Union Road, CB2 1EZ, UK (fax: +44-1223-336033;
e-mail: deposit@ccdc.cam.ac.uk) and are available on request
quoting the deposition numbers CCDC
).
The colorless crystals of 11b (C24H31N5O4) are monoclinic. At
293 K a = 7.585(1), b = 31.462(1), c = 9.803(2) Å, ꢁ =
91.98(1)º, V = 2338(1) Å3, Mr = 453.57, Z = 4, space group
P21/n, dcalc= 1.289 g/cm3, μ(MoKꢂ) = 0.090 mm-1, F(000) = 968.
Intensities of 13830 reflections (5317 independent, Rint =0.039)
were measured on the «Xcalibur-3» diffractometer (graphite
monochromated MoKꢂ radiation, CCD detector, ꢃ-scaning,
2ꢄmax = 55°). The structure was solved by direct method using
SHELXTL package [38]. Position of the hydrogen atoms were
located from electron density difference maps and refined by
“riding” model with Uiso = 1.2Ueq of carrier atom. Full-matrix
least-squares refinement against F2 in anisotropic approximation
using 5278 reflections was converged to wR2 = 0.097 (R1
=
0.042 for 2420 reflections with F>4ꢀ(F), S = 0.785. The final
atomic coordinates, and crystallographic data for molecule 11b
have been deposited to the Cambridge Crystallographic Data
Centre, 12 Union Road, CB2 1EZ, UK (fax: +44-1223-336033;
e-mail: deposit@ccdc.cam.ac.uk) and are available on request
quoting the deposition numbers CCDC).
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Sep-Oct 2008
Synthesis, structure and some reactions of new partially hydrogenated
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1427
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