1,3-Dipolar cycloadditions to (5Z)-1-Acyl-5-(cyanomethylidene)-imidazolidine-2,4-diones: Synthesis and transformations of spirohydantoin derivatives

Article abstract of DOI:10.1002/1522-2675(20011114)84:11<3403::AID-HLCA3403>3.0.CO;2-G

Cycloadditions of various 1,3-dipoles to (5Z)-1-acyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-diones 8 or 9, prepared in 3 steps from hydantoin (1) (Schemes 1 and 2), were studied. In all cases, reactions proceeded regio- and stereoselectively. The type of product depended on the 1,3-dipole and/or dipolarophile employed as well as on reaction conditions. Thus, with stable dipoles under neutral conditions, spirohydantoin derivatives 12-16 were obtained (Scheme 2), while under basic or acidic conditions, pyrazole- or isoxazole-5-carboxamides 18 and 23-26 and carboxylate 27 were formed via aromatization of the newly formed dihydroazole ring, followed by the simultaneous cleavage of the hydantoin ring (Schemes 3-5).

Full text of DOI:10.1002/1522-2675(20011114)84:11<3403::AID-HLCA3403>3.0.CO;2-G

Helvetica Chimica Acta Vol. 84 (2001)
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1,3-Dipolar Cycloadditions to (5Z)-1-Acyl-5-(cyanomethylidene)-
imidazolidine-2,4-diones: Synthesis and Transformations of Spirohydantoin
Derivatives
by Urosœ Grosœelja), Alesœ Drobnicœ a), Simon Recœnika), Jurij Svetea)*, Branko Stanovnika)*, Amalija Golobicœ a),
Nina Laha), Ivan Lebana), Anton Medena), and Simona Golicœ-Grdadolnikb)
a) Faculty of Chemistry and Chemical Technology, University of Ljubljana,
œ
œ
Askerceva 5, SI-1000 Ljubljana
b) National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana
Cycloadditions of various 1,3-dipoles to (5Z)-1-acyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-
diones 8 or 9, prepared in 3 steps from hydantoin (1) (Schemes 1 and 2), were studied. In all cases, reactions
proceeded regio- and stereoselectively. The type of product depended on the 1,3-dipole and/or dipolarophile
employed as well as on reaction conditions. Thus, with stable dipoles under neutral conditions, spirohydantoin
derivatives 12 16 were obtained (Scheme 2), while under basic or acidic conditions, pyrazole- or isoxazole-5-
carboxamides 18 and 23 26 and carboxylate 27 were formed via aromatization of the newly formed
dihydroazole ring, followed by the simultaneous cleavage of the hydantoin ring (Schemes 3 5).
Introduction. There are several examples of naturally occurring and synthetic
hydantoin (ˆ imidazolidine-2,4-dione) derivatives exhibiting various biological activ-
ities, such as antitumor [1][2], antiarrhythmic [3], anticonvulsant [4], and herbicidal [5]
activity, inhibition of glycogen phosphorylase [6] and aldose reductase [7], and
neurotransmission [8] effects. Examples of such compounds are aplysinopsin [1][8][9],
hydantocidin and its analogs [5 7], and tetrantoin [4] ( Fig. 1).
Fig. 1. Hydantoin derivatives exhibiting biological activities.
On the other hand, 2-substituted alkyl 3-(dimethylamino)prop-2-enoates, 2-
substituted alkyl 3-cyanoprop-2-enoates, and their cyclic analogs are easily available
and proved to be efficient reagents for the preparation of various heterocyclic systems
[10]. In this connection, 2-substituted alkyl 3-cyanoprop-2-enoates and their chiral
cyclic analogs were employed as dipolarophiles in 1,3-dipolar cycloaddition reactions
leading to pyrazoles, isoxazoles, and their fused and spiro analogs [11][12]. Recently,
we reported a simple and stereoselective synthesis of aplysinopsin analogs, which

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employs 3-(dimethylamino)-2-(vinylamino)prop-2-enoate and 5-[(dimethylamino)-
methylidene]hydantoin derivatives as the key intermediates [13]. As an extension of
our work in this field towards the synthesis of spirohydantoins, we report the
preparation of (5Z)-1-acetyl-5-(cyanomethylidene)-3-methylimidazolidine- 2,4-dione
(8) and (5Z)-1-benzoyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-dione (9)
and their transformations with various 1,3-dipoles.
Results and Discussion. The starting compounds (5Z)-5-(dimethylamino)meth-
ylidene]imidazolidine-2,4-dione (2) and (5Z)-5-(dimethylamino)methylidene]-3-
methylimidazolidine-2,4-dione (3) were prepared from hydantoin (1) according to
the procedures described previously [13] (Scheme 1). Treatment of compounds 2 or 3
with KCN in AcOH at room temperature gave the corresponding (2Z)-2-(2,5-
dioxoimidazolidin-4-ylidene)acetonitrile (4) and (2Z)-2-(1-methyl-2,5-dioxoimid-
azolidin-4-ylidene)acetonitrile (5) in 70% yield. The (Z)-configuration of the exocyclic
CˆC bond in compound 5 was established by X-ray analysis (see Fig. 2). Treatment of
imidazolidinylideneacetonitriles 4 or 5 with excess CH2N2 (7) furnished, in both cases,
the same product, (2Z)-2-(1,3-dimethyl-2,5-dioxoimidazolidin-4-ylidene)acetonitrile
(6) in quantitative yield.
Since no cycloadduct was formed upon reaction of 4 or 5 with excess CH2N2 (7),
compound 5 was transformed into its 1-acetyl and 1-benzoyl derivatives 8 and 9,
respectively, to increase the dipolarophilicity of the exocyclic CˆC bond. These 1-acyl
derivatives 8 and 9 were then treated with the following 1,3-dipoles: CH2N2 (7), the
azomethine imine (1Z)-5,5-dimethyl-3-oxo-1-[(2,4,6-trimethoxyphenyl)methylidene]-
pyrazolidin-1-ium-2-ide (10), and 2,4,6-trimethoxybenzonitrile N-oxide (11a). In all
cases, compounds 8 and 9 underwent regioselective 1,3-dipolar cycloaddition reactions
to give the corresponding spirocyclic adducts. Thus, reaction of 8 and 9 with excess
CH2N2 (7) afforded rel-(4R,5R)-6-acetyl-8-methyl-7,9-dioxo-1,2,6,8-tetraazaspiro[4.4]-
non-1-ene-4-carbonitrile (12) and its 6-benzoyl analog 13 in 66 and 74% yield,
Scheme 1
i) t-BuOCH(NMe2)2, MeCN, reflux, 1 ! 2. ii) Me2NCH(OMe)2, MeCN, reflux, 1 ! 3. iii) KCN, AcOH, r.t. iv)
CH2N2 (7), Et2O, À108 r.t.

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Fig. 2. ORTEP View of the asymmetric unit of compound 5 with labelling (arbitrary) of non-H-atoms. Ellipsoids
are at 50% probability level.
respectively. Similarly, 1,3-dipolar cycloaddition of azomethine imine 10 to dipolar-
ophiles 8 and 9 took place upon microwave irradiation in refluxing 1,4-dioxane to give
the corresponding rel-(1R,2R,3S)-3'-acyl-1',5,5-trimethyl-2',5',7-trioxo-3-(2,4,6-tri-
methoxyphenyl)spiro[1H,5H]pyrazolo[1,2-a]pyrazole-1,4'-imidazolidine]-2-carbonitrile
14 and 15, respectively, in moderate yields. Finally, treatment of the dipolarophile 8
with 2,4,6-trimethoxybenzonitrile N-oxide (11a) in CHCl3 under reflux gave rel-
(4R,5S)-6-acetyl-8-methyl-7,9-dioxo-3-(2,4,6-trimethoxyphenyl)-1-oxa-2,6,8-triaza-
spiro[4.4]non-2-ene-4-carbonitrile (16a) in 73% yield (Scheme 2).
The relative configuration around the C(2)ÀC(3) single bond in cycloadduct 14 was
established by NMR. The coupling constant (J(HÀC(2), HÀC(3)) ˆ 10àHz) was not
in good agreement with the reported values for related di- and perhydropyrazoles (J ˆ
3 10 Hz for cis-configuration; J ˆ 10 14 Hz for trans-configuration) [14]. Since no
NOE effect was observed between HÀC(2) and HÀC(3), we supposed that these two
1
protons were trans-oriented. In the H-NMR spectrum of compound 14, the MeO
groups of the 2,4,6-trimethoxyphenyl substituent were nonequivalent (3s, each 3 H).
The distances between HÀC(2) and HÀC(3) and the corresponding nearest ortho-
MeO groups of the aryl residue were determined by NOESY technique. The results
(d(HÀC(2) ¥¥¥ MeO) ˆ d(HÀC(3) ¥¥¥ MeO) ˆ 0.32 nm) were in agreement with the
proposed configuration (Fig. 3).
Furthermore, the structures of 12, 14 and 16a were confirmed by X-ray diffraction
(Figs. 4 6).
On the other hand, reaction of 1-benzoyl derivative 9 with 2,4,6-trimethoxybenzo-
nitrile N-oxide (11a) and 2,4,6-trimethylbenzonitrile N-oxide (11b) in CHCl3 under
reflux furnished the corresponding N-[(benzoylamino)carbonyl]isoxazol-5-carboxa-
mides 18a,b (Scheme 3). Analogously, the N-[(acylamino)carbonyl]-1H-pyrazol-5-

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Scheme 2
i) Ac2O, pyridine, r.t., 5 ! 8. ii) PhCOCl, pyridine, r.t., 5 ! 9. iii) CH2N2 (7), Et2O, CHCl3, À108 À r.t. iv) (1Z)-
5,5-dimethyl-3-oxo-1-[(2,4,6-trimethoxyphenyl)methylidene]pyrazolidin-1-ium-2-ide (10), 1,4-dioxane, micro-
‡
wave (1000 W), reflux. v) 2,4,6-(MeO)3C6H2CꢀN ÀOÀ (11a), CHCl3, reflux.
Fig. 3. Configuration of 14

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Fig. 4. ORTEP View of the asymmetric unit of compound 12 with labelling (arbitrary) of non-H-atoms.
Ellipsoids are at 50% probability level.
Fig. 5. ORTEP Stereoview of the asymmetric unit of compound 14 with labelling (arbitrary) of non-H-atoms.
Ellipsoids are at 50% probability level.
carboxamides 23a and 24a were obtained upon treatment of dipolarophiles 8 and 9 with
4-chloro-N-phenylbenzonitrile imine (20a), formed in situ from 4-chloro-N-phenyl-
benzenecarbohydrazonoyl chloride (19a) and Ag2O, in CH2Cl2 at room temperature.

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Helvetica Chimica Acta Vol. 84 (2001)
Fig. 6. ORTEP View of the asymmetric unit of compound 16a with labelling (arbitrary) of non-H-atoms.
Ellipsoids are at 50% probability level.
The structure of compound 18b was determined by X-ray-analysis (Fig. 7). According
to our previous results in the acyclic 2-(acylamino)-3-cyanoprop-2-enoate series,
formation of the N-[(acylamino)carbonyl]carboxamides 18a,b, 23a, and 24a could be
rationalized by initial formation of primary spiro cycloadducts 17a,b, 21a, and 22a,
respectively, followed by isomerization leading to opening of the hydantoin ring and
aromatization of the isoxazoline or pyrazoline rings [11].
However, when the reactions of 8 with benzenecarbohydrazonoyl chlorides 19a,b
were carried out in the presence of Et3N in CH2Cl2 under reflux or in the presence of
Ag2O in MeCN under reflux, the carboxamides 25a,b were obtained (Scheme 4).
Presumably also in this case, spiro compounds 21a,b were formed first, followed by
isomerization to the N-[(acetylamino)carbonyl]carboxamides 23a,b as intermediates,
from which, under slightly more drastic conditions, MeCONCO was eliminated to give
pyrazole-5-carboxamides 25a,b. This reaction sequence was supported by independent
experiments, where 23a and 18b were treated with Et3N in refluxing CH2Cl2 to give the
carboxamides 25a and 26b, respectively (Scheme 4).
Heating compound 8 with nitrile oxides 11a c in CHCl3 followed by purification of
the crude mixture by column chromatography (CC; silica gel, CHCl3/MeOH 100 :1)
afforded the corresponding methyl 3-aryl-4-cyanoisoxazole-3-carboxylates 27a c
(Scheme 5). Apparently, silica-gel-catalyzed methanolysis took place during chromato-
graphic purification with the MeOH-containing eluent. To establish which possible
intermediates could be involved in the reaction mechanism, additional experiments
were carried out. First, passing the spiro compound 16a through a silica-gel-filled

Helvetica Chimica Acta Vol. 84 (2001)
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Scheme 3
‡
‡
i) 2,4,6-(MeO)3C6H2ꢀN ÀOÀ (11a) or 2,4,6-Me3C6H2CꢀN ÀOÀ (11b), CHCl3, reflux. ii) 4-ClC6H4C(Cl)ˆ
NNHPh (19a), Ag2O, CH2Cl2, r.t.
Fig. 7. ORTEP View of the asymmetric unit of compound 18b with labelling (arbitrary) of non-H-atoms.
Ellipsoids are at 50% probability level.

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Scheme 4
i) 4-ClC6H4C(Cl)ˆNNHPh (19a) or 4-MeC6H4C(Cl)ˆNNHPh (19b), Et3N, CH2Cl2, reflux (G.P. A). ii) 19a,
Ag2O, MeCN, reflux (G.P. B). iii) Et3N, CH2Cl2, reflux (G.P. C).
column with CHCl3/MeOH as eluent furnished isoxazole-5-carboxylate 27a (Scheme 5,
Path A). Then, under the same conditions, isoxazole-5-carboxylate 27a and benzamide
28 were obtained from N-[(benzoylamino)carbonyl]carboxamide 18a (Path B). On the
other hand, isoxazole-5-carboxamide 26b was not transformed into methyl isoxazole-5-
carboxylate 27b upon passing through a silica-gel-filled column with CHCl3/MeOH as
eluent (Path C). These experiments might indicate that the formation of methyl
isoxazole-5-carboxylates 27 proceeds via spiro compounds 16 and/or N-[(acylamino)-
carbonyl]carboxamides 18 followed by silica-gel-catalyzed transacylation into 27
(Paths A and B, resp.), although isoxazole-5-carboxamides 26 (Path C) still cannot be
excluded as possible intermediates.

Scheme 5
‡
‡
‡
i) 2,4,6-(MeO)3C6H2CꢀN ÀOÀ (11a), 2,4,6-Me3C6H2CꢀN ÀOÀ (11b), or 2,6-Cl2C6H3CꢀN ÀOÀ (11c), CHCl3, reflux, then CC (CHCl3/MeOH 100 :1) (G.P. A). ii)
CC (CHCl3/MeOH 100 :1) (G.P. B).

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Conclusion.
The (5Z)-1-acyl-5-(cyanomethylidene)imidazolidine-2,4-diones 8
and 9 are easily available precursors for the preparation of various spirohydantoin
derivatives 12 16 by 1,3-dipolar cycloadditions to various 1,3-dipoles under mild and/
or neutral conditions. However, reactions of 8 and 9 with nitrile oxides and nitrile
imines under more drastic conditions, such as upon heating or in the presence of a base
or an acid, furnished 3-aryl-4-cyanoisoxazole- or 3-aryl-4-cyano-1H-pyrazole-5-carbox-
ylic acid derivatives 18 and 23 27. According to experimental evidence, these reactions
might proceed via isomerization of the initially formed spirohydantoins 16, 17, and 21
into N-[(acylamino)carbonyl]carboxamides 18, 23, and 24, followed by transformation
into substituted isoxazole- or 1H-pyrazole-5-carboxylic acid derivatives 25 27. The
relative ease of isomerization of spirohydantoins to the N-[(acylamino)carbonyl]-
carboxamides could be explained by the tendency for aromatization of the newly
formed dihydroisoxazole or dihydro-1H-pyrazole ring (see, e.g., Scheme 3) which is
achieved by elimination of the amide moiety resulting in opening of the hydantoin ring.
Experimental Part
General. (5Z)-5-[(Dimethylamino)methylidene]imidazolidine-2,4-dione (2), (5Z)-5-[(dimethylamino)-
methylidene]-3-methylimidazolidine-2,4-dione (3) [13], CH2N2 (7) [15], (1Z)-5,5-dimethyl-3-oxo-1-[(2,4,6-
trimethoxyphenyl)methylidene)]pyrazolidin-1-ium-2-ide (10) [16], 2,4,6-trimethoxybenzonitrile N-oxide (11a),
2,4,6-trimethylbenzonitrile N-oxide (11b), 2,6-dichlorobenzonitrile N-oxide (11c) [17], 4-chloro-N-phenyl-
benzenecarbohydrazonoyl chloride (19a), and 4-methyl-N-phenylbenzenecarbohydrazonoyl chloride (19b) [18]
were prepared according to the published procedures. All starting materials were commercially available (in
most cases from Fluka) and purified by standard techniques. Column chromatography (CC): silica gel 60 (0.04
0.063 mm, Fluka). TLC: alu foils coated with silica gel 60 F 254 (0.2 mm, Merck). Microwave irradiation:
Milestone LAVIS-1000 laboratory microwave oven with a reflux condenser. M.p.: Kofler micro hot stage. IR:
Perkin-Elmer Spectrum-BX-FTIR and Perkin-Elmer 1310 spectrometers; KBr pellets; in cmÀ1. 1H- (300 MHz)
and 13C-NMR (75.5 MHz): Bruker Avance-DPX 300 spectrometer; d in ppm rel. to Me4Si as internal standard
(ˆ0 ppm), J in Hz. MS: in m/z. Elemental analyses: Perkin-Elmer CHN Analyser 2400. MS: Autospeck Q (VG-
Analytical) spectrometer.
(2Z)-2-(2,5-Dioxoimidazolidin-4-ylidene)acetonitrile (4). A soln. of KCN (0.358 g, 5.5 mmol) in a soln. of 2
(0.775g, 5mmol) in AcOH (10 ml) was left at r.t. for 2 days. Volatile components were evaporated, and the
residue was purified by CC (AcOEt/hexane 1:1): 4 (0.481 g, 70%). M.p. 194 1968. IR: 2210 (CꢀN), 1770, 1700
(CˆO). 1H-NMR ((D6)DMSO): 5.43 (s, CHCN); 11.66 (br. s, NH). 13C-NMR ((D6)DMSO): 73.09; 116.6;
146.0; 155.5; 163.9. Anal. calc. for C5H3N3O2 (137.10): C 43.80, H 2.21, N 30.65; found: C 43.68, H 2.06, N 50.51.
(2Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)acetonitrile (5). A soln. of KCN (0.715g, 11 mmol) in a
soln. of 3 (1.690 g, 10 mmol) in AcOH (20 ml) was left at r.t. for 2 days. Volatile components were evaporated,
the residue was dissolved in H2O (20 ml), the soln. left at r.t. for 24 h, and the precipitate collected by filtration:
5 (1.056 g, 70%). M.p. 186 1888. IR: 2200 (CꢀN), 1780, 1730 (CˆO). 1H-NMR ((D6)DMSO): 2.91 (s,
MeÀN(1)); 5.57 (s, CHCN); 11.91 (br. s, HÀN(3)). 13C-NMR ((D6)DMSO): 25.2; 74.1; 116.4; 145.0; 155.2;
162.7. Anal. calc. for C6H5N3O2 (151.12): C 47.69, H 3.33, N 27.81; found: C 47.33, H 3.20, N 27.54.
(2Z)-2-(1,3-Dimethyl-2,5-dioxoimidazolidin-4-ylidene)acetonitrile (6). A cold soln. (0 58) of diazo-
methane (7) in Et2O (ca. 0.2m, 15ml, ca. 3 mmol) was added to a soln. of 4 or 5 (1 mmol) in THF (10 ml) at
À108, and the soln. was left at À108 for 12 h. Volatile components were left to evaporate in a ventilated hood to
1
give 6 (0.166 g, 99%). M.p. 108 1108. IR: 2200 (CꢀN), 1710, 1760 (CˆO). H-NMR ((D6)DMSO): 2.95( s,
MeÀN(1)); 3.35( s, Me À N(3)); 5.67 (s, CHCN). 13C-NMR ((D6)DMSO): 25.9; 28.4; 73.9; 116.8; 144.2; 155.2;
162.2. Anal. calc. for C7H7N3O2 (165.15): C 50.91, H 4.27, N 25.44; found: C 50.53, H 4.43, N 25.48.
(5Z)-1-Acetyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-dione (8). Ac2O (3.6 ml, 36 mmol) was
added to a soln. of 4 (1.812 g, 12 mmol) in anh. pyridine (5ml), and the soln. was left at r.t. for 2 h. The mixture
was poured into a mixture of ice (20 ml), H2O (20 ml), and AcOH (5ml), and the precipitate was collected by
filtration to give 8 (1.657 g, 72%). M.p. 124 1268. IR: 2200 (CꢀN), 1780, 1700 (CˆO). 1H-NMR ((D6)DMSO):

Helvetica Chimica Acta Vol. 84 (2001)
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2.58 (s, MeCO); 3.00 (s, MeÀN(3)); 6.20 (s, CHCN). Anal. calc. for C8H7N3O3 (193.16): C 49.74, H 3.65, N
21.75; found: C 49.67, H 3.45, N 21.40.
(5Z)-1-Benzoyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-dione (9). As described for 8, with
PhCOCl (0.35ml, 3 mmol), 5 (0.507 g, 3 mmol), and pyridine (1 ml) for 3.5 h. Workup with ice (5 ml), H2O
(5ml), and AcOH (1 ml). The precipitate was washed with EtOH (5ml): 9 (0.265 g, 35%). M.p. 159 1608. IR:
1
2220 (CꢀN), 1790, 1720 (CˆO). H-NMR ((D6)DMSO): 2.96 (s, MeÀN(3)); 6.27 (s, CHCN); 7.55 7.60 (m,
2 arom. H); 7.72 7.78 (m, 1 arom. H); 7.95 7.98 ( m, 2 arom. H). Anal. calc. for C13H9N3O3 (255.23): C 61.18, H
3.55, N 16.46; found: C 60.91, H 3.58, N 16.05.
rel-(4R,5R)-6-Acetyl-8-methyl-7,9-dioxo-1,2,6,8-tetraazaspiro[4.4]non-1-ene-4-carbonitrile (12). A soln. of
diazomethane (7) in Et2O (ca. 0.4m, 10 ml, ca. 4 mmol) was added to a soln. of 8 (0.193 g, 1 mmol) in CH2Cl2
(7 ml). After 12 h at r.t., heptane was added slowly with stirring until the soln. became slightly turbid. The more
volatile components (mostly Et2O and CH2Cl2) were left to evaporate in a well-ventilated hood to 1/2 of the
initial volume (ca. 10 ml). The precipitate was filtered off and washed with Et2O: 12 (0.145g, 66%). M.p. 143
1458. IR: 2230 (CꢀN), 1710, 1790 (CˆO). 1H-NMR ((D6)DMSO): 2.54 (s, MeCO); 3.07 (s, MeÀN(8)); 3.65
(dd, J ˆ 6.8, 9.5, HÀC(4)); 5.12 (dd, J ˆ 6.8, 18.8, 1 HÀC(3)); 5.48 (dd, J ˆ 9.8, 18.8, 1 HÀC(3)). 13C-NMR
((D6)DMSO): 25.5; 26.7; 27.9; 84.2; 103.5; 117.2; 153.6; 166.5; 169.5. Anal. calc. for C9H9N5O3 (235.20): C 45.96,
H 3.86, N 29.78; found: C 45.70, H 3.65, N 29.60.
rel-(4R,5R)-6-Benzoyl-8-methyl-7,9-dioxo-1,2,6,8-tetraazaspiro[4.4]non-1-ene-4-carbonitrile (13). A soln.
of diazomethane (7) in Et2O (ca. 0.5m, 16 ml, ca. 8 mmol) was added to a soln. of 9 (0.255 g, 1 mmol) in CHCl3
(10 ml), and the solution was left at r.t. for 12 h. The precipitate was filtered off and washed with Et2O: 13
(0.220 g, 74%). M.p. 180 1828. IR: 2240 (CꢀN), 1800, 1730 1680 (CˆO). 1H-NMR ((D6)DMSO): 3.05( s,
MeÀN(8)); 3.85( dd, J ˆ 6.8, 9.4, HÀC(4)); 5.23 (dd, J ˆ 6.8, 18.8, 1 HÀC(3)); 5.54 (dd, J ˆ 9.8, 18.8,
1 HÀC(3)); 7.47 7.52 (m, 2 arom. H); 7.60 7.65( m, 1 arom. H); 7.67 7.69 (m, 2 arom. H). 13C-NMR
((D6)DMSO): 26.8; 27.4; 84.4; 104.3; 117.0; 128.7; 129.5; 133.4; 134.2; 152.8; 166.5; 168.6. Anal. calc. for
C14H11N5O3 (297.27): C 56.56, H 3.73, N 23.56; found: C 56.70, H 3.73, N 23.64.
Cycloadducts 14 and 15: General Procedure. A mixture of dipolarophile 8 or 9 (0.5mmol), azomethine
imine 10 (0.322 g, 1.1 mmol), and anh. 1,4-dioxane (15ml) was irradiated under reflux in a laboratory
microwave oven (P ˆ 1000 W, pulse width 0.1 s) for 1.5 2.5h. Volatile components were evaporated, and the
residue was purified by CC. Nonpolar impurities were eluted with AcOEt/hexane 2 :1 followed by elution of the
product with AcOEt: spiro compounds 14 and 15, resp.
rel-(1R,2R,3S)-3'-Acetyl-1',5,5-trimethyl-2',5',7-trioxo-3-(2,4,6-trimethoxyphenyl)spiro[1H,5H-pyrazo-
lo[1,2-a]pyrazole-1,4'-imidazolidine]-2-carbonitrile (14). From 8 (1.5h): 0.320 g (66%). M.p. 259 262 8 (CHCl3/
hexane). IR: 2250 (CꢀN), 1800, 1730, 1680 (CˆO). 1H-NMR (CDCl3): 0.87, 1.38 (2s, 1:1, 2 MeÀC(5)); 2.30 (d,
J ˆ 16.2, 1 HÀC(6)); 2.68 (s, MeCO); 2.71 (d, J ˆ 16.2, 1 HÀC(6)); 3.19 (s, MeÀN(1')); 3.83, 3.89, 3.92 (3s,
1:1:1, 3 MeO); 5.42 (d, J ˆ 10.0, HÀC(2)); 5.73 (d, J ˆ 10.0, HÀC(3)); 6.16 (s, 2 arom. H). 13C-NMR (CDCl3):
20.7; 25.8; 25.9; 26.3; 42.7; 50.7; 53.2; 55.4; 56.1; 56.5; 61.5; 72.3; 91.2; 92.4; 101.3; 114.8; 152.6; 160.5; 161.7;
162.4; 163.9; 167.1; 169.3. Anal. calc. for C23H27N5O7 (485.49): C 56.90, H 5.61, N 14.43; found: C 56.92, H 5.64, N
14.25.
rel-(1R,2R,3S)-3'-Benzoyl-1',5,5-trimethyl-2',5',7-trioxo-3-(2,4,6-trimethoxyphenyl)spiro[1H,5H-pyrazo-
lo[1,2-a]pyrazole-1,4'-imidazolidine]-2-carbonitrile (15). From 9 (2.5h): 0.224 g (41%). M.p. 210 212 8 (CHCl3/
hexane). IR: 2250 (CꢀN), 1810, 1740, 1710 (CˆO). 1H-NMR (CDCl3): 0.88, 1.35(2 s, 1:1, MeÀC(5)); 2.33 (d,
J ˆ 16.2, 1 HÀC(6)); 2.77 (d, J ˆ 16.2, 1 HÀC(6)); 3.17 (s, MeÀN(1')); 3.84, 3.90, 3.94 (3s, 1 :1:1, 3 MeO); 5.51
(d, J ˆ 10.2, HÀC(2)); 5.82 (d, J ˆ 10.2, HÀC(3)); 6.17 (s, 2 arom. H); 7.42 7.47 (m, 2 arom. H); 7.52 7.58 (m,
1 arom. H); 7.72 7.75( m, 2 arom. H). Anal. calc. for C28H29N5O7 (547.56): C 61.42, H 5.34, N 12.79; found: C
61.62, H 5.42, N 13.08.
rel-(4R,5S)-6-Acetyl-8-methyl-7,9-dioxo-3-(2,4,6-trimethoxyphenyl)-1-oxa-2,6,8-triazaspiro[4.4]non-2-ene-
4-carbonitrile (16a). A mixture of 8 (0.147 g, 0.76 mmol), nitrile oxide 11a (0.159 g, 0.76 mmol), and CHCl3
(5ml) was refluxed for 4 h. The mixture was evaporated to 1/2 of the initial volume, and heptane ( ca. 2 ml) was
added slowly with stirring until the soln. became slightly turbid. Crystallization was induced by scratching, and
the precipitate was filtered off: 16a (0.082 g, 20%). M.p. 176 1788 (heptane/CHCl3). IR: 2230 (CꢀN), 1810,
1740 (CˆO). 1H-NMR (CDCl3): 2.62 (s, MeCO); 3.21 (s, MeÀN(8)); 3.86, 3.91 (2s, 1 :2, 3 MeO); 5.55 (s,
HÀC(4)); 6.21 (s, 2 arom. H). 13C-NMR (CDCl3): 25.5; 26.0; 48.4; 55.6; 56.5; 91.6; 92.0; 96.2; 112.1; 147.1; 152.0;
160.8; 164.1; 167.0; 168.5. Anal. calc. for C18H18N4O7 (402.36): C 53.73, H 4.51, N 13.92; found: C 53.47, H 4.59, N
13.72.
N-[(Benzoylamino)carbonyl]isoxazole-5-carboxamides 18a,b: General Procedure. A mixture of 9 (0.255 g,
1 mmol), nitrile oxide 11a,b (1 mmol), and CHCl3 (10 ml) was refluxed for 3 4 h. Volatile components were

3414
Helvetica Chimica Acta Vol. 84 (2001)
partially evaporated to 1/2 of the initial volume (ca. 5ml) and heptane was added slowly until an oil separated;
the oil crystallized upon scratching. The precipitate was filtered off: carboxamides 18a,b.
N-[(Benzoylamino)carbonyl]-4-cyano-N-methyl-3-(2,4,6-trimethoxyphenyl)isoxazole-5-carboxamide
(18a). From 11a (4 h): 0.305g (66%). M.p. 147 150 8 (AcOEt/hexane). IR: 3206 (NH), 2248 (CꢀN), 1773,
1655 (CˆO). 1H-NMR (CDCl3): 3.61 (s, MeN); 3.84, 3.89 (2s, 2 :1, 3 MeO); 6.23 (s, 2 arom. H); 7.51 7.56 (m,
2 arom. H); 7.60 7.66 (m, 1 arom. H); 7.96 7.99 (m, 2 arom. H); 12.22 (s, NH). 13C-NMR (CDCl3): 33.6; 56.0;
56.4; 91.4; 95.1; 102.3; 110.0; 128.2; 129.5; 132.9; 133.9; 149.2; 158.7; 160.0; 160.4; 164.7; 164.8; 166.0. Anal. calc.
for C23H20N4O7 (464.43): C 59.48, H 4.34, N 12.06; found: C 59.70, H 4.04, N 11.83.
N-[(Benzoylamino)carbonyl]-4-cyano-N-methyl-3-(2,4,6-trimethylphenyl)isoxazole-5-carboxamide (18b).
From 11b (3 h): 0.259 g (62%). M.p. 145 1818 (AcOEt/hexane). IR: 3201 (NH), 2250 (CꢀN), 1780, 1760
1
(CˆO). H-NMR (CDCl3): 2.15, 2.34 (2s, 2 :1, 3 arom. Me); 3.62 (s, MeN); 7.00 (s, 2 arom. H); 7.50 7.55 (m,
2 arom. H); 7.60 7.63 (m, 1 arom. H); 7.95 7.97 ( m, 2 arom. H); 12.05( s, NH). Anal. calc. for C23H20N4O4
(416.43): C 66.34, H 4.84, N 13.45; found: C 66.52, H 4.73, N 13.26.
1H-Pyrazole-5-carboxamides 23a and 24a: General Procedure. Ag2O (0.281 g, 1.21 mmol) was added to a
soln. of 8 or 9 (1 mmol) and hydrazonoyl chloride 19a (0.265g, 1 mmol) in CH 2Cl2 (11 ml), and the mixture was
stirred at r.t. for 1 3 h. After filtration and evaporation, the residue was purified by CC: carboxamides 23a and
24a, resp.
N-[(Acetylamino)carbonyl]-3-(4-chlorophenyl)-4-cyano-N-methyl-1-phenyl-1H-pyrazole-5-carboxamide
(23a). From 8 (1 h; CC (Et2O)): 0.359 g (85%). M.p. 167 1708 (CH2Cl2/hexane). IR: 3272 (NÀH), 2236
(CꢀN), 1748, 1713, 1662 (CˆO). 1H-NMR (CDCl3): 2.45( s, MeCO); 3.17 (s, MeN); 7.47 7.57 (m, 7 arom. H);
7.99 8.03 (m, 2 arom. H); 10.78 (s, NH). 13C-NMR (CDCl3): 26.1; 33.6; 91.9; 112.6; 123.8; 128.1; 128.5; 129.8;
‡
130.5; 130.6; 136.9; 138.2; 142.0; 150.5; 152.9; 163.2; 171.7. EI-MS: 421 ( M ). Anal. calc. for C21H16 ClN5O3
(421.84): C 59.79, H 3.82, N 16.60; found: C 59.69, H 3.72, N 16.23.
N-[(Benzoylamino)carbonyl]-3-(4-chlorophenyl)-4-cyano-1-phenyl-1H-pyrazole-5-carboxamide (24a).
From 9 (3 h; CC (CH2Cl2/petroleum ether/Et2O 10 :2 :1)): 0.394 g (81%). M.p. 143 1458 (CH2Cl2/hexane).
IR: 3207 (NÀH), 2236 (CꢀN), 1780, 1657 (CˆO). 1HÀNMR (CDCl3): 3.17 (s, MeN); 7.48 7.66 (m, 10 arom.
H); 7.95 8.05( m, 4 arom. H); 12.17 (s, NH). 13C-NMR (CDCl3): 33.6; 92.2; 112.5, 123.5; 128.1; 128.3; 128.5;
129.5; 129.8; 130.7, 130.7; 132.93; 133.9; 136.9; 138.1; 141.8; 148.9; 153.1; 164.2; 164.7. Anal. calc. for C 26H16
ClN5O3 (483.91): C 64.53, H 3.75, N 14.47; found: C 64.55, H 3.60, N 14.08.
1H-Pyrazole-5-carboxamides 25a,b. General Procedure A (G.P. A). Et3N (0.05ml, 0.36 mmol) was added
to a soln. of 8 (0.038 g, 0.2 mmol) and hydrazonoyl chloride 19a,b (0.2 mmol) in CH2Cl2 (4 ml), and the mixture
was refluxed for 3 4 h. Volatile components were evaporated, and the residue was purified by CC (Et2O) and
crystallization from i-Pr2O/CHCl3: carboxamides 25a,b.
General Procedure B (G.P. B). Ag2O (0.213 g, 0.92 mmol) was added to a soln. of 8 (0.089 g, 0.46 mmol)
and hydrazonoyl chloride 19a (0.122 g, 0.46 mmol) in MeCN (7 ml), and the mixture was refluxed for 3 h. The
mixture was then cooled and filtered, the filtrate evaporated, and the residue purified by CC (Et2O):
carboxamide 25a.
General Procedure C (G.P. C). Et3N (0.14 ml, 1.4 mmol) was added to a soln. of 23a (0.084 g, 0.2 mmol) in
CH2Cl2 (5ml), and the mixture was refluxed for 3 h. Volatile components were evaporated, and the residue was
purified by CC (Et2O): carboxamide 25a.
3-(4-Chlorophenyl)-4-cyano-N-methyl-1-phenyl-1H-pyrazole-5-carboxamide (25a). From 19a and Et3N
(3 h, G.P. A). 0.026 g (40%): From 19a and Ag2O (G.P. B). 0.109 g (70%). From 23a and Et3N (G.P. C): 0.050 g
(74%). M.p. 218 2218 (CHCl3/i-Pr2O). IR: 3290 (NÀH), 2240 (CꢀN), 1660 (CˆO). 1H-NMR ((D6)DMSO):
2.79 (d, J ˆ 4.9, MeN); 7.51 7.59 (m, 5arom. H); 7.64 7.69 ( m, 2 arom. H); 7.95 7.99 ( m, 2 arom. H); 9.17 (q,
J ˆ 4.9, NH). 13C-NMR ((D6)DMSO): 27.1; 91.4; 114.0; 124.5; 129.1; 129.3; 130.2; 130.3; 130.4; 135.6; 138.9;
145.6; 151.5; 158.5. Anal. calc. for C18H13ClN4O (336.77): C 64.19, H 3.89, N 16.64; found: C 64.51, H 3.69, N
16.40.
4-Cyano-N-methyl-3-(4-methylphenyl)-1-phenyl-1H-pyrazole-5-carboxamide (25b). From 9 and Et3N (4 h,
G.P. A): 0.017 g (27%). M.p. 207 2118 (CHCl3/i-Pr2O). IR: 3260 (NÀH), 2230 (CꢀN), 1650 (CˆO). 1H-NMR
((D6)DMSO): 2.39 (s, 1 arom. Me); 2.79 (d, J ˆ 4.9, MeN); 7.38 7.40 (m, 2 arom. H); 7.52 7.58 (m, 5arom. H);
7.83 7.86 (m, 2 arom. H); 9.15( q, J ˆ 4.9, NH). Anal. calc. for C19H16N4O (316.36): C 72.13, H 5.10, N 17.71;
found: C 72.13, H 5.07, N 17.67.
4-Cyano-N-methyl-3-(2,4,6-trimethylphenyl)isoxazole-5-carboxamide (26b) Solvate with Heptane 3 :1. Et3N
(0.1 ml, 0.71 mmol) was added to a soln. of 18b (0.060 g, 0.144 mmol) in CH2Cl2 (3 ml), and the mixture was
heated under reflux for 2 h. Volatile components were evaporated, and the residue was purified by CC (AcOEt/
petroleum ether 1:3). The product was crystallized from CH2Cl2/heptane: 3 26b ¥ C7H16 (0.033 g, 76%). M.p.

Helvetica Chimica Acta Vol. 84 (2001)
3415
1
127 1298. IR: 3356 (NH), 2251 (CꢀN), 1671 (CˆO). H-NMR (CDCl3): 0.88 (br. t, 2 Me of heptane); 1.27
(br., 5CH 2 of heptane); 2.14, 2.34 (2s, 2 :1, 3 arom. Me); 3.11 (d, J ˆ 5.3, MeN); 6.62 (br. s, NH); 6.98 (s, 2 arom.
H). 13C-NMR (CDCl3) 26b: 20.3; 21.6; 26.9; 97.7; 109.6; 121.4; 129.3; 137.6; 141.2; 154.5; 164.4; 167.4; heptane:
14.5; 23.1; 26.9; 29.4; 32.3. Anal. calc. for C52H61N9O6 (908.10): C 68.78, H 6.77, N 13.88; found: C 69.22, H 6.48,
‡
2
N 13.69. HR-MS: 269.117770 C15H15N3O ; calc. 269.117050.
Methyl Isoxazole-5-carboxylates 27a c and Benzamide 28. General Procedure (G.P. A). A mixture of 8
(0.193 g, 1 mmol) and nitrile oxide 11a c (1 mmol) in CHCl3 (15ml) was stirred at r.t. or reflux for 3 h or 3 days.
Volatile components were evaporated, and the residue was purified by CC (CHCl3/MeOH 100 :1). The product
was dissolved in petroleum ether (ca. 20 ml), and the soln. was left at À158 for 12 h. The precipitate was filtered
off: methyl isoxazole-5-carboxylates 27a c.
General Procedure (G.P. B). Compound 16a (0.113 g, 0.28 mmol) or 18a (0.066 g, 0.14 mmol) was passed
through a silica gel filled column with CHCl3/MeOH 100 :1 as eluent. Fractions containing the products 27a and
28 were combined and evaporated in vacuo. Each residue was dissolved in hexane (ca. 10 ml), and the soln. was
left at À158 for 12 h. Each precipitate was filtered off: methyl isoxazole-5-carboxylate 27a and benzamide 28,
resp.
Methyl 4-Cyano-3-(2,4,6-trimethoxyphenyl)isoxazole-5-carboxylate (27a). From 11a (reflux, 5h; G.P. A):
0.181 g (57%). From 16a (G.P. B): 0.062 g (69%). From 18a (G.P. B): 0.040 g (88%). M.p. 149 1518 (petroleum
ether). IR: 2250 (CꢀN), 1740 (CˆO). 1H-NMR (CDCl3): 3.82, 3.87 (2s, 2 :1 3 arom. Me); 4.07 (s,
MeOOCÀC(5)); 6.21 (s, 2 arom. H). 13C-NMR (CDCl3): 54.0; 55.9; 56.3; 91.2; 95.8; 101.0; 110.2; 155.7; 158.8;
160.0; 163.3; 164.5. Anal. calc. for C15H14N2O6 (318.28): C 56.60, H 4.43, N 8.80; found: C 56.92, H 4.48, N 8.62.
Methyl 4-Cyano-3-(2,4,6-trimethylphenyl)isoxazole-5-carboxylate (27b). From 11b (reflux, 3 h; G.P. A):
1
0.216 g (80%). M.p. 76 778 (petroleum ether). IR: 2250 (CꢀN), 1740 (CˆO). H-NMR (CDCl3): 2.14, 2.34
(2s, 2 :1, 3 arom. Me); 4.11 (s, MeOOCÀC(5)); 6.98 (s, 2 arom. H). Anal. calc. for C15H14N2O3 (270.28): C 66.66,
H 5.22, N 10.36; found: C 66.97, H 5.28, N 10.37.
Methyl 4-Cyano-3-(2,6-dichlorophenyl)isoxazole-5-carboxylate (27c). From 11c (r.t., 3 days; G.P. A):
0.133 g (45%). M.p. 89 918 (petroleum ether). IR: 2250 (CꢀN), 1730 (CˆO). 1H-NMR (CDCl3): 4.12 (s,
MeOOC); 7.44 7.53 (m, 3 arom. H). Anal. calc. for C12H6Cl2N2O3 (297.09): C 48.51, H 2.04, N 9.43; found: C
48.73, H 2.02, N 9.17.
N-[(Methylamino)carbonyl]benzamide (28). From 18a (G.P. B): 0.022 g (86%). M.p. 164 1698 ([19]: m.p.
170 1718). IR: 3332 (NH), 1702, 11678 (CˆO). 1H-NMR (CDCl3): 2.96 (d, J ˆ 4.9, Me); 7.47 7.52 (m, 2 arom.
H); 7.57 7.63 (m, 1 arom. H); 7.90 7.94 (m, 2 arom. H); 8.59 (br. s, MeNH); 8.97 (s, CONH).
X-Ray Crystal-Structure Analyses for Compounds 5, 12, 14, 16a, and 18b. Diffraction data for compounds 5
and 12 were collected on an Enraf-Nonius-CAD4 and for 14, 16a, and 18b on a Nonius Kappa CCD
diffractometer. Graphite monochromated MoKa radiation was used in all cases. For 5 and 12 intensities of
reflections were corrected for Lorentz-polarization effects, and decay with the Xtal3.4 [20] program package.
Data for 14, 16a, and 18b were processed with the DENZO [21] program. Due to low values of the linear
absorption coefficients for all five compounds, no absorption correction was applied. Structures were solved by
direct methods: 5, 12, and 14 with the SIR97 [22] and 16a and 18b with the SHELX-97 [23] program. For the
structures of 5, 12, and 14, we employed full-matrix least-squares refinement on F magnitudes with anisotropic
displacement factors for all non-H-atoms using Xtal3.4 [20]. The positions of H-atoms of 5 and 12 were
obtained from the difference Fourier map. Most of the H-atoms of 14 were also located by means of difference
Fourier map, the remaining were calculated by means of expected geometry. The parameters of H-atoms of
compounds 5 and 14 were not refined in the final refinement, while those of compound 12 were refined
isotropically with restrained CÀH bonds. In the final cycle of the refinement, we used 936, 1957, and 3387
reflections, and 100, 181, and 317 parameters for 5, 12, and 14, respectively. The number of restraints for 12 was
29. Structures 16a and 18b were refined by full-matrix least-squares on F2 with SHELX-97 [23]. Non-H-atoms
were refined anisotropically; H-atoms were placed at ideal positions with the displacement parameters taken as
1.2 times (aromatic) and 1.5times (methyl) of their parent atoms. The resulting crystal data and details
concerning data collection and refinement for all five compounds are given in the Table. The crystallographic
data for compounds 5, 12, 14, 16a, and 18b have also been deposited with the Cambridge Crystallographic Data
Center as supplementary material with the deposition numbers CCDC 162165, CCDC 162166, CCDC 162167,
CCDC 162168, and CCDC 162169, resp. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.
The asymmetric units of compounds 5, 12, 14, 16a, and 18b are presented in Figs. 2 and 4 7, resp. Figs. 2, 4,
and 5 were prepared with the aid of ORTEP-II [24] and Figs. 6 and 7 with ORTEP-III [25]. In the structure of
compound 5, the molecules are nearly planar. They are connected via intermolecular NH ¥¥¥ O H-bonds: the

3416
Helvetica Chimica Acta Vol. 84 (2001)
Table 1. Crystal Data, Data Collection, and Structure Refinement for Compounds 5, 12, 14, 16a, and 18b
5
12
14
16a
18
Formula
Mr
C6H5N3O2
151.14
C9H9N5O3
235.2
C23H27N5O7
485.5
C18H18N4O7
402.36
C23H20N4O4
416.43
Crystal system
Space group
a [ä]
b [ä]
c [ä]
a [8]
b [8]
g [8]
V [ä3]
Z
orthorhombic
P212121, No. 19 P21/n, No. 14
5.934(1)
6.223(1)
18.073(1)
90.00
90.00
90.00
667.39(16)
4
1.504
monoclinic
triclinic
monoclinic
P21/n, No. 14
14.0062(3)
9.3111(2)
14.9528(3)
90.00
111.1870(10)
90.00
1826.02(7)
4
monoclinic
P21/c, No. 14
15.2342(3)
7.21270(10)
19.2387(5)
90.00
105.2210(7)
90.00
2039.79(7)
4
P-1, No. 2
8.3590(2)
10.4270(2)
15.2693(4)
72.5466(11)
84.4195(10)
70.6496(12)
1197.87(5)
2
5.5300(6)
13.549(1)
14.600(1)
90.00
95.788(7)
90.00
1088.34(16)
4
1.435
0.112
293(1)
Enraf Nonius
CAD4
28.0
1 [Mg mÀ3
]
1.346
0.101
150(1)
1.464
0.1150.095
200(1)
1.356
m [mmÀ1
T [K]
]
0.117
293(1)
Enraf Nonius
CAD4
28.0
6483
972
150(1)
Diffractometer
Nonius Kappa Nonius Kappa Nonius Kappa
CCD
27.525 27.5
9643
5494
CCD
CCD
qmax [8]
Total refl.
.0
6299
2617
1960
5871
3142
2710
F2 > 2.0s (F2)
0.036, 0.088
0.0001
16357
4662
3091
F2 > 2.0s (F2)
0.0532, 0.1393
0.048
Independent refl.
Observed refl.
Threshold criterion
Final R and Rw
(D/s)max
884
3387
I
net > 2.5s (Inet
)
I
net > 2.5s (Inet
)
F2 > 2.0s (F2)
0.047, 0.053
0.0002
0.032, 0.033
0.0004
0.048, 0.031
0.024
Rint
0.013
0.187, À0.176
0.014
0.245, À0.321
0.030
0.507, À0.555
0.0181
0.350, À0.167
0.0558
0.316, À0.273
D1max, D1min [e äÀ3
]
N(1) . .O(4) contact distance is 2.876(2) ä and N(1)ÀH ¥¥¥ O(4) angle is 176.8(1)8. The configuration about the
C(5)ˆC(7) bond is Z. Molecules of 12, 14, and 16a are chiral, but the corresponding solid-state compounds are
racemates. The molecules of 18b are twisted about the C(3)ÀC(30) and C(5)ÀC(11) bonds. An intramolecular
contact of the NÀH ¥¥¥ O type with the N(12) . .O(11) contact distance of 2.596(1) ä is present in these
molecules. Bond lengths and angles of all five compounds are within expected ranges and in agreement with the
values reported for related structures [26].
The financial support from the Ministry of Science and Technology, Slovenia, is gratefully acknowledged.
The crystallographic data for three compounds were collected on the Kappa-CCD-Nonius diffractometer in the
Laboratory of Inorganic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana,
Slovenia; we acknowledge the financial contribution of the Ministry of Science and Technology through grants
X-2000 and PS-511-103 which made the purchase of the diffractometer possible.
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Received April 23, 2001