1,3-Thiazolidine-dicarboxylates from thioketones and thermally generated azomethine ylides

Article abstract of DOI:10.1002/1522-2675(200207)85:7<2056::AID-HLCA2056>3.0.CO;2-O

The reaction of 9H-fluorene-9-thione (1) with the cis- and trans-isomers of dimethyl 1-(4-methoxyphenyl)- Saziridine-2,3-dicarboxylate (cis- and trans-2, resp.) in xylene at 110° yielded exclusively the spirocyclic cycloadduct with trans- and cis-configurations, respectively (trans- and cis-3; resp.; Scheme 1). Analogously, less-reactive thioketones, e.g., thiobenzophenone (5), and cis-2 reacted stereoselectively to give the corresponding trans-1,3-thiazolidine-2,4-dicarboxylate (e.g., trans-8; Scheme 2). On the other hand, the reaction of 5 and trans-2 proceeded in a nonstereoselective course to provide a mixture of trans- and cis-substituted cycloadducts. This result can be explained by an isomerization of the intermediate azomethine ylide. Dimethyl 1,3-thiazolidine-2,2-dicarboxylates 14 and 15 were formed in the thermal reaction of dimethyl aziridine-2,2-dicarboxylate 11 with aromatic thioketones (Scheme 3). On treatment of 14 and 15 with Raney-Ni in refluxing EtOH, a desulfurization and ring-contraction led to the formation of azetidine-2,2-dicarboxylates 17 and 18, respectively (Scheme 4).

Full text of DOI:10.1002/1522-2675(200207)85:7<2056::AID-HLCA2056>3.0.CO;2-O

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Helvetica Chimica Acta Vol. 85 (2002)
1,3-Thiazolidine-dicarboxylates from Thioketones and Thermally
Generated Azomethine Ylides
by Grzegorz Mloston¬* and Katarzyna Urbaniak1)
¬
¬
¬
¬
Section of Heteroorganic Compounds, University of Ëodz, Narutowicza 68, PL-90-136 Ëodz
and Heinz Heimgartner*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
Dedicated to Professor Waldemar Adam on the occasion of his 65th birthday
The reaction of 9H-fluorene-9-thione (1) with the cis- and trans-isomers of dimethyl 1-(4-methoxyphenyl)-
aziridine-2,3-dicarboxylate (cis- and trans-2, resp.) in xylene at 1108 yielded exclusively the spirocyclic
cycloadduct with trans- and cis-configurations, respectively (trans- and cis-3, resp.; Scheme 1). Analogously, less-
reactive thioketones, e.g., thiobenzophenone (5), and cis-2 reacted stereoselectively to give the corresponding
trans-1,3-thiazolidine-2,4-dicarboxylate (e.g., trans-8; Scheme 2). On the other hand, the reaction of 5 and trans-
2 proceeded in a nonstereoselective course to provide a mixture of trans- and cis-substituted cycloadducts. This
result can be explained by an isomerization of the intermediate azomethine ylide. Dimethyl 1,3-thiazolidine-2,2-
dicarboxylates 14 and 15 were formed in the thermal reaction of dimethyl aziridine-2,2-dicarboxylate 11 with
aromatic thioketones (Scheme 3). On treatment of 14 and 15 with Raney-Ni in refluxing EtOH,
a
desulfurization and ring-contraction led to the formation of azetidine-2,2-dicarboxylates 17 and 18, respectively
(Scheme 4).
Introduction. Saturated 1,3-thiazole carboxylates are compounds of considerable
importance, as some representatives show interesting biological activities. Special
attention is focused on 1,3-thiazolidine-4-carboxylates and -2,4-dicarboxylates [1 3].
This type of 1,3-thiazole derivatives can be used as building blocks in the synthesis of
pharmaceuticals such as immunomodulating drugs (cf. [3] and refs. cit. therein) or
antibiotics (cf. [4]). Some examples of dipeptides containing 1,3-thiazolidine-4-
carboxylic acid have also been prepared [3][5].
The most frequently used method for the synthesis of 1,3-thiazolidine carboxylates
is based on cyclocondensation reactions of cysteine with carbonyl compounds. For
example, 1,3-thiazolidine-2,4-dicarboxylic acid was prepared starting from glyoxylic
acid [1]. Retrosynthetic analysis leads to the conclusion that 1,3-dipolar cycloaddition
of azomethine ylides substituted by ester groups with CˆS dipolarophiles should offer
convenient and stereocontrolled access to this class of compounds. This concept has
already been explored by Gallagher and co-workers for the synthesis of penam and
penem skeletons [6].
One method that can be used to generate appropriate azomethine ylides is the
stereoselective thermal ring opening of aziridine-carboxylates. For example, aziridine-
1
¬
¬
Part of the planned Ph. D. thesis of K.U., University of Ëodz.
)

Helvetica Chimica Acta Vol. 85 (2002)
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2,3-dicarboxylates were used by Huisgen and co-workers to demonstrate the scope of
orbital symmetry rules [7]2). Furthermore, 1,3-diarylaziridine-2,2-dicarboxylates are
also well-known as convenient precursors of azomethine ylides [9]. Although
azomethine ylides belong to the most extensively explored class of 1,3-dipoles [10],
reactions with CˆS dipolarophiles were rarely reported. One of the reasons seems to
be the instability of many thioketones and thioaldehydes. In recent years, however,
sterically crowded and relatively stable thioketones have been prepared and success-
fully applied in syntheses of S heterocycles [11]. Within the last decade, we have
reported on 1,3-dipolar cycloadditions of differently generated azomethine ylides with
thiocarbonyl compounds [12 15].
The topic of the present paper are reactions of aromatic thioketones with aziridine
dicarboxylates leading to 1,3-thiazolidine-dicarboxylates. Furthermore, a novel ring
contraction of the five-membered products to azetidine-dicarboxylates is presented.
Results and Discussion. As 9H-fluorene-9-thione (1) easily undergoes dimeriza-
tion in a hetero-Diels-Alder fashion [16], the reaction with aziridines required modified
conditions compared with typical procedures for analogous reactions [12]: a solution of
1 was added in small portions to a heated solution of the respective aziridine. After each
addition, the color of 1 disappeared immediately. As soon as 0.9 equiv. of 1 had been
added to a solution of cis-2 or trans-2 (Scheme 1), the solvent was evaporated, and the
1
crude residue was examined by H-NMR spectroscopy. In each case, a single product
was detected, showing two singlets at 6.08/5.00 and 5.67/4.95 ppm, respectively. The
products were isolated after chromatographic workup in 50 and 23% yield3), and
characterized as spiro-1,3-thiazolidines trans-3 and cis-3, respectively. The relative
configurations were assigned on the basis of the observation that conrotatory ring
opening of cis-2 leads stereoselectively to the azomethine ylide s-trans-4; trans-2 is the
precursor of s-cis-4 [7][13], and the cycloaddition proceeds suprafacially.
The reactions of thiobenzophenone (5), 9H-xanthene-9-thione (xanthione, 6), and
9H-thioxanthene-9-thione (thioxanthione, 7) with aziridines cis-2 or trans-2 were
carried out in toluene at 908 (Scheme 2). The mixtures were heated until the color of
5 7 disappeared. With cis-2, the formation of a single product was observed in all
cases; therefore, the reactions occurred with complete stereoselectivity to give 1,3-
thiazolidines trans-8, trans-9, and trans-10 with the ester groups in a trans relationship.
In contrast to this result, the reactions of 5 and 6 carried out with trans-2 under the
same condition led to mixtures of trans-8 and trans-9, respectively, together with their
diastereoisomers, i.e., the expected cis-configured cycloadducts cis-8 and cis-9. The cis/
1
trans ratio determined in the crude mixture by H-NMR spectroscopy was ca. 4 :1 in
both cases. The lower selectivity observed in the reactions of trans-2 corresponds to
similar results reported for reactions with several C,C dipolarophiles [17]4) and 1,3-
thiazole-5(4H)-thiones [13]. Apparently, the azomethine ylide s-cis-4 undergoes an
2
)
The cis- and trans-isomers of dimethyl 1-(4-methoxyphenyl)aziridine-2,3-dicarboxylate were the preferred
models in the investigation of the thermal and photochemical electrocyclic ring opening of aziridines to
azomethine ylides [7] and the equilibration of the stereoselectively formed 1,3-dipoles [8].
Small amounts of the yellow dimer of 1 were separated as a less-polar fraction.
For a kinetics study, see [18].
3
4
)
)

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 1
Scheme 2

Helvetica Chimica Acta Vol. 85 (2002)
2059
isomerization (rotation around the NÀC bond) to give s-trans-4, when less-reactive
dipolarophiles are involved. In the case of the least reactive 7 with trans-2, no formation
of a cycloadduct was observed.
For the preparation of 1,3-thiazolidine-2,2-dicarboxylates, thioketones 1 and 5 were
reacted with dimethyl 1,3-diphenylaziridine-2,2-dicarboxylate (11) (Scheme 3). This
aziridine was prepared in situ by thermolysis of dimethyl 4,5-dihydro-1,5-diphenyl-1H-
1,2,3-triazole-4,4-dicarboxylate 12a [9]5). In both cases, with 1 and 5, a regioselective
formation of the corresponding 1,3-thiazolidine 14 and 15, respectively, was observed.
After chromatographic workup and crystallization, pure cycloadducts were obtained,
and the structure of 14 has been established by X-ray crystallography [20]. The result
shows that C(2) bears the two ester groups, and Ph is attached to C(4). By comparison
of spectral data, the analogous regioisomer was assigned to cycloadduct 15.
Scheme 3
To examine the earlier reported structure of adduct 16 of adamantanethione and
the azomethine ylide generated from 11 [12] in the light of the present results, 16 was
resynthesized under the conditions described above. Crystals of 16 suitable for X-ray
5
)
Whereas the generation of 11/13 from 12a is well-documented [9], similar access to N-alkyl-substituted
analogues is unknown. Recently, the N-methyl derivative 12b has been prepared and used in thermal
reactions as a potential precursor of the corresponding azomethine ylide, but in none of the experiments
was any evidence for the intermediacy of this dipole found [19]. To examine other N-alkyl derivatives of
type 12, we pepared compounds 12c and d with a Bu and PhCH2 substituent, respectively, at N(1) by [3 ‡ 2]
cycloaddition of the corresponding azides with dimethyl benzylidenemalonate. On the basis of the
13C-NMR data, the analogous structure to 12a was ascribed to the new 4,5-dihydro-1,2,3-triazoles 12c and
12d. Both compounds were heated in xylene (1308), but no evolution of N2 was observed. Furthermore, on
heating in the presence of thiobenzophenone (5), the blue color of 5 did not disappear even after a few
hours.

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crystal-structure determination were obtained from MeOH, and the analysis showed
that, in this case, the cycloaddition occurred with the opposite regioselectivity
compared with those shown in Scheme 3 [20]. Based on this observation, we conclude
that cycloadditions of azomethine ylide 13 with aromatic and cycloaliphatic thioke-
tones proceed with opposite regioselectivity. The same difference is well-documented
for 1,3-dipolar cycloadditions of aromatic thioketones and adamantane-thione with
thiocarbonyl ylides [21][22].
The 1,3-thiazolidines described above were used as models to study desulfurization
processes of saturated five-membered S heterocycles. The reagent most frequently used
for desulfurization is Raney-Ni, and its applications have been reviewed [23]. In a
typical manner, a solution of 14 or 15 in MeOH/CH2Cl2 was stirred at room
temperature with a portion of Raney-Ni, until TLC showed complete conversion of
starting materials. In each case, only one product, 17 or 18, respectively, was formed.
1
The H-NMR spectra showed a similar set of signals as observed for 14 or 15. For
example, the spectrum of 17 formed from 14 was characterized by a singlet at 6.97 ppm
‡
(1 H) and two singlets for MeO at 3.60 and 2.99 ppm. The [M ‡ 1] peak (CI-MS) was
registered at m/z 478, indicating that the product differs from 14 by one S-atom. All
spectroscopic data are in accordance with the structure of azetidine derivatives 17 and
18.
Scheme 4
To the best of our knowledge, conversions of 1,3-thiazolidines to azetidines via
desulfurization have never been reported. Numerous 1,3-thiazole derivatives by
treatment with Raney-Ni were desulfurized to give open-chain N-containing products
[23]. The above-described formation of azetidines depends strongly on the structure of
the starting material. Attempted desulfurization of 16 was unsuccessful, and the
starting material was recovered. In the case of trans-8, a mixture of unidentified
products was obtained. Our results show that the substitution pattern of the 1,3-
thiazolidine ring is crucial for the conversion into azetidine derivatives.
We thank the analytical sections of our institutes for spectra and elemental analyses and Dr. Jaroslaw
¬
Romanski and Mr. Radoslaw Szymanski for performing preliminary experiments. Financial support of the

Helvetica Chimica Acta Vol. 85 (2002)
2061
Polish State Committee for Scientific Research (Grant No. 3 TO9A 00716), the Swiss National Science
Foundation, and F. Hoffmann-La Roche AG, Basel, is gratefully acknowledged.
Experimental Part
1. General. See [24]. 9H-Fluorene-9-thione (1) was prepared from 9H-fluorene-9-one and P4S10 as reported
by Lawesson and co-workers [16]. Thiobenzophenone (5), 9H-xanthene-9-thione (xanthione, 6), and 9H-
thioxanthene-9-thione (thioxanthione, 7) were obtained by thionation of the corresponding ketones with
Lawesson×s reagent [25]. Dimethyl cis- and trans-1-(4-methoxyphenyl)aziridine-2,3-dicarboxylate (cis- and
trans-2) were obtained according to a modified procedure reported by Szeimies and Huisgen [26]. Dimethyl 1,3-
diphenylaziridine-2,2-dicarboxylate (11) was prepared in situ by thermal extrusion of N2 from 4,5-dihydro-1,5-
diphenyl-1H-1,2,3-triazole-4,4-dicarboxylate (12a) [9].
2. Reactions of 1 with Aziridine Dicarboxylates 2 and 11. a) A soln. of 1 (196 mg, 1.0 mmol) and cis- or trans-
2 (258.5 mg, 1.1 mmol) in 2 ml of toluene were heated to 1108 (oil bath). After 1 h, the olive-green color of 1
disappeared, the solvents were evaporated, the crude residues were analyzed by 1H-NMR spectroscopy, and the
products were separated by column chromatography (CC, SiO2) with a mixture of petroleum ether and
increasing amounts of CH2Cl2 as eluant. Anal. pure products were obtained by recrystallization from an
appropriate solvent.
b) A soln. of 12a (373 mg, 1.1 mmol) in 1 ml of xylene was heated under magnetic stirring to 1308 (oil bath).
After 30 min, the evolution of N2 ceased and the soln. containing 11 was used directly for further experiments.
The temp. of the oil bath was reduced to ca. 1108, and a soln. of 1 (196 mg, 1.0 mmol) in 1 ml of xylene was added
in small portions within ca. 30 min. When the addition was complete, heating was continued for ca. 30 min.
Dimethyl trans-3'-(4-Methoxyphenyl)spiro[9H-fluorene-9,5'-[1,5]thiazolidine]-2',4'-dicarboxylate (trans-3).
Reaction with cis-2. Yield: 215 mg (50%). M.p. 179 1808 (MeOH). IR (KBr): 750s, 1039m, 1173s, 1201s,
1248m, 1448m, 1512s, 1736vs (CˆO), 1755vs (CˆO). 1H-NMR: 3.32, 3.70, 3.77 (3s, 3 MeO); 4.97, 6.06 (2s,
HÀC(2'), HÀC(4')); 6.79 (br. s, 4 arom. H); 7.17 7.83 (m, 8arom. H). 13C-NMR: 52.8, 53.3, 55.7 (3q, 3 MeO);
62.8( s, C(5')); 64.3, 74.7 (2d, C(2'), C(4')); 114.7, 119.4, 119.6, 120.0, 125.3, 126.0, 127.4, 128.7, 128.9, 129.4 (10d,
12 arom. CH); 138.2, 140.6, 141.6, 150.8, 154.6 (5d, 6 arom. C); 169.6, 171.3 (2s, 2 CˆO). CI-MS: 462 (85, [M ‡
‡
1] ), 358(38), 254 (51), 226 (100), 196 (22), 194 (36). Anal. calc. for C 26H23NO5S (461.54): C 67.66, H 5.02,
N 3.03, S 6.95; found: C 66.99, H 5.04, N 3.00, S 6.89.
Dimethyl cis-3'-(4-Methoxyphenyl)spiro[9H-fluorene-9,5'-[1,3]thiazolidine]-2',4'-dicarboxylate (cis-3). Re-
action with trans-2. Yield: 128mg (28%). M.p. 166 167 8 (MeOH). IR (KBr): 764s, 8 17m, 1040s, 1170vs, 1249vs,
1288vs, 1406s, 1510s, 1762vs (br). 1H-NMR: 3.23, 3.76, 3.83 (3s, 3 MeO); 4.94, 5.66 (2s, HÀC(2'), HÀC(4'));
6.83 6.95 (m, 4 arom. H); 7.25 7.67 (m, 8arom. H). 13C-NMR: 51.6, 52.8, 55.5 (3q, 3 MeO); 63.5 (s, C(5'));
65.8, 74.9 (2d, C(2'), C(4')); 114.7, 119.3, 119.6, 119.9, 123.8, 126.8, 127.8, 128.3, 128.9, 129.0 (10s, 12 arom. CH);
‡
139.3, 139.4, 139.7, 143.4, 146.9 (5s, 6 arom. C); 168.5, 170.3 (2s, 2 CˆO). CI-MS: 462 (100, [M ‡ 1] ), 358(41),
335 (16), 256 (28), 254 (34), 226 (82). Anal. calc. for C26H23NO5S (461.54): C 67.66, H 5.02, N 3.03, S 6.95;
found: C 67.60, H 5.07, N 3.22, S 6.78.
Dimethyl 3',4'-Diphenylspiro[9H-fluorene-9,5'-[1,3]thiazolidine]-2',2'-dicarboxylate (14). Reaction with
12a. Yield (after CC): 210 mg (42%). M.p. 200 2018 (MeOH). IR (KBr): 700s, 731s, 750s, 1124m, 1257vs,
1
1450m, 1493m, 1734vs (CˆO), 1761s (CˆO). H-NMR: 3.42, 3.85 (2s, 2 MeO); 5.95 (s, HÀC(4')); 6.50 8.30
(m, 18arom. H). 13C-NMR: 52.8, 53.2 (2q, 2 MeO); 64.4 (s, C(5')); 77.0 (s, C(2')); 78.7 (d, C-(4')); 119.0, 119.8,
125.3, 125.6, 126.4, 126.5, 126.9, 127.4, 127.6, 128.0, 128.3, 129.0 (12d, 18arom. CH); 133.7, 139.0, 141.3, 143.4,
‡
‡
144.2, 147.7 (6s, 6 arom. C); 168.9, 169.6 (2s, 2 CˆO). CI-MS: 508(33, [ M ‡ 1] ), 476 (5, [M À MeO] ), 346
(32), 312 (100), 224 (22), 197 (17), 182 (32). Anal. calc. for C31H25NO4S (506.60): C 73.49, H 4.77, N 2.76, S 6.33;
found: C 73.52, H 4.80, N 2.87, S 5.98.
3. Reaction of 5 with 11. The reaction was carried out as described in 2, b). Dimethyl 3,4,5,5-Tetraphenyl-1,3-
thiazolidine-2,2-dicarboxylate (15). Yield: 320 mg (63%). M.p. 152 1548 (MeOH) ([12]: 153 1558). IR (KBr):
746m, 1254vs, 1313s, 1444m, 1504s, 1599m, 1738vs (CˆO). 1H-NMR: 3.18, 3.98 (2s, 2 MeO); 6.18( s, HÀC(4));
6.60 7.85 (m, 20 arom. H). 13C-NMR: 52.8, 53.7 (2q, 2 MeO); 69.7 (s, C(5)); 74.0 (d, C(4)); 77.3 (s, C(2)); 113.5,
117.8, 119.7, 127.0, 127.2, 127.4, 127.8, 128.2, 129.1, 129.2, 129.5, 130.1 (12d, 20 arom. CH); 138.2, 140.2, 143.6, 144.4
(4s, 4 arom. C); 168.6, 168.7 (2s, 2 CˆO).
4. Reactions of 5, 6, and 7 with Dimethyl Aziridine-2,3-dicarboxylates 2. General Procedure. A soln. of
aziridine 2 (282 mg, 1.1 mmol) in 1 ml of toluene was heated (oil bath) under magnetic stirring to 908. After
10 min, a soln. of 1 mmol of thioketone in 1 ml of toluene was added. The flask was equipped with a condenser,

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Helvetica Chimica Acta Vol. 85 (2002)
and the heating was continued until complete consumption of the thioketone (TLC). The solvent was removed
i.v., and the crude mixtures were analyzed by 1H-NMR spectroscopy. Pure products were isolated after
crystallization or CC (SiO2) with a mixture of petroleum ether and increasing amounts of CH2Cl2. Anal. pure
products were obtained by recrystallization from an appropriate solvent.
4.1. Reactions with cis-2. With Thiobenzophenone (5). Reaction time 20 h; the 1H-NMR spectrum revealed
the presence of only one product showing 2 s for CH at 5.55 and 5.62 ppm. Crystallization from MeOH afforded
345 mg (71%) of dimethyl trans-3-(4-methoxyphenyl)-5,5-diphenyl-1,3-thiazolidine-2,4-dicarboxylate (trans-8).
Colorless prisms. M.p. 126 1278. IR (KBr): 698m, 1041m, 1173s, 1196s, 1259s, 1444w, 1514s, 1734vs (CˆO),
1751vs (CˆO). 1H-NMR: 3.08, 3.32, 3.70 (3s, 3 MeO); 5.55, 5.62 (2s, HÀC(2), HÀC(4)); 6.45 6.97 (m, 4 arom.
H); 7.08 7.57 ( m, 10 arom. H). 13C-NMR: 51.7, 52.4, 55.7 (3q, 3 MeO); 63.9, 73.1 (2d, C(2), C(4)); 66.7 (s,
C(5)); 115.4, 115.6, 127.1, 128.1, 128.2, 128.3, 129.2 (7d, 14 arom. CH); 139.1, 139.9, 146.7, 153.8(4 s, 4 arom. C);
‡
170.7, 171.3 (2s, 2 CˆO). CI-MS: 464 (100, [M ‡ 1] ), 422 (17), 360 (30). Anal. calc. for C26H25NO5S (463.55):
C 67.37, H 5.43, N 3.02, S 6.92; found: C 66.99, H 5.47, N 3.07, S 6.81.
With 9H-Xanthene-9-thione (6). Reaction time 30 h; the 1H-NMR spectrum revealed the presence of only
one product showing 2s for CH at 5.03 and 5.98ppm. CC (SiO 2) led to 175 mg (34%) of dimethyl trans-3'-(4-
methoxyphenyl)spiro[9H-xanthene-9,5'-[1,3]thiazolidine]-2',4'-dicarboxylate (trans-9). Colorless crystals.
M.p. 183 1858. IR (KBr): 756m, 1039w, 1171s, 1196s, 1246vs, 1319m, 1444s, 1477s, 1512s, 1736vs (CˆO),
1759s (CˆO). 1H-NMR: 3.05, 3.67, 3.72 (3s, 3 MeO); 5.03, 5.98(2 s, HÀC(2'), HÀC(4')); 6.65 6.85 (m, 4 arom.
H); 6.92 7.42 (m, 8arom. H). 13C-NMR: 51.7, 52.5, 55.5 (3q, 3 MeO); 59.0 (s, C(5')); 66.3, 80.7 (2d, C(2'),
C(4')); 114.8, 116.3, 121.7, 121.8, 123.1, 123.9, 129.6, 129.9, 130.9, 131.1 (10d, 12 arom. CH); 125.0, 138.8, 151.2,
‡
151.3, 155.9 (5s, 6 arom. C); 168.8, 171.6 (2s, 2 CˆO). CI-MS: 478(100, [ M ‡ 1] ), 374 (35), 266 (16), 213 (66).
Anal. calc. for C26H23NO6S (477.54): C 65.39, H 4.85, N 2.93, S 6.72; found: C 65.08, H 5.00, N 2.98, S 6.85.
1
With 9H-Thioxanthene-9-thione (7). Reaction time 24 h; the H-NMR spectrum revealed the presence of
only one product showing 2s for CH at 5.45 and 5.90 ppm. Crystallization from MeOH afforded 7 mg (14%) of
dimethyl trans-3'-(4-methoxyphenyl)spiro[9H-thioxanthene-9,5'-[1,3]thiazolidine]-2',4'-dicarboxylate (trans-
10). Colorless crystals. M.p. 178 179 8. IR (KBr): 750m, 1030m, 1170s, 1250s, 1430m, 1500s, 1745vs (CˆO).
1H-NMR: 3.00, 3.65, 3.80 (3s, 3 MeO); 5.45, 5.90 (2s, HÀC(2'), HÀC(4')); 6.33-6.83 (m, 4 arom. H); 7.08 7.67
(m, 8arom. H). 13C-NMR: 51.4, 52.8, 55.6 (3q, 3 MeO); 63.7, 72.8(2 d, C(2'), C(4')); 66.7 (s, C(5')); 115.0, 119.1,
126.6, 126.7, 127.4, 128.1, 128.2, 128.5, 131.5, 132.2 (10d, 12 arom. CH); 134.5, 135.5, 137.7, 139.0, 154.9 (5s, 6 arom.
‡
C); 170.1, 170.7 (2s, 2 CˆO). CI-MS: 494 (77, [M ‡ 1] ), 462 (7), 390 (9), 266 (50), 229 (100), 196 (44). Anal.
calc. for C26H23NO5S2 (493.60): C 63.26, H 4.69, N 2.84, S 12.99; found: C 62.64, H 4.73, N 2.85, S 13.05.
4.2. Reactions with trans-2. With 5. Reaction time 10 h; the 1H-NMR spectrum of the reaction mixture
indicated the presence of cis-8 and trans-8 in a ratio of ca. 4 :1. The main product was separated as the more polar
fraction after CC (SiO2, petroleum ether/CH2Cl2): Dimethyl cis-3-(4-Methoxyphenyl)-5,5-diphenyl-1,3-thi-
azolidine-2,4-dicarboxylate (cis-8). Yield: 60 mg (24%). Colorless crystals. M.p. 117 1188 (MeOH). IR (KBr):
1740vs (CˆO). 1H-NMR: 3.25, 3.74, 3.76 (3s, 3 MeO); 5.22, 5.26 (2s, HÀC(2), HÀC(4)); 6.56 6.87 (m, 5 arom.
H); 7.01 7.36 (m, 8arom. H). 13C-NMR: 51.8, 52.9, 55.6 (3q, 3 MeO); 62.7, 73.3 (2d, C(2), C(4)); 67.5 (s, C(5));
114.0, 115.1, 126.8, 127.1, 128.0, 128.1, 128.3, 128.8 (8d, 14 arom. CH); 138.5, 138.6, 145.8, 152.9 (4s, 4 arom. C);
‡
169.3, 170.6 (2s, 2 CˆO). CI-MS: 464 (100, [M ‡ 1] ), 360 (63), 266 (22), 256 (29), 239 (37). Anal. calc. for
C26H25NO5S (463.55): C 67.37, H 5.43, N 3.02, S 6.92; found: C 67.03, H 5.43, N 3.01, S 6.88.
With 6. Reaction time 37 h; the 1H-NMR spectrum of the crude product indicated the presence of cis-9 and
trans-9 in a ratio of ca. 4 :1. CC gave the main product as the more polar fraction.
Dimethyl cis-3'-(4-Methoxyphenyl)spiro[9H-xanthene-9,5'-[1,3]thiazolidine]-2',4'-dicarboxylate (cis-9).
Yield: 105 mg (22%). Colorless prisms. M.p. 151 1528 (MeOH). IR (KBr): 749s, 1039s, 1183vs, 1205vs,
1249vs, 1270s, 1445vs, 1475s, 1510vs, 1600m, 1749vs (CˆO), 1757vs (CˆO). 1H-NMR: 3.10, 3.67, 3.80 (3s, 3
MeO); 4.62, 5.73 (2s, HÀC(2'), HÀC(4')); 6.57 6.88 (m, 4 arom. H); 6.93 7.50 (m, 8arom. H). 13C-NMR: 51.7,
52.9, 55.6 (3q, 3 MeO); 59.5, 81.0 (2d, C(2'), C(4')); 68.2 (s, C(5')); 114.9, 116.2, 121.1, 121.8, 123.4, 123.8, 129.4,
129.5, 129.9, 131.2 (10d, 12 arom. CH); 125.6, 139.5, 151.4, 151.8, 156.1 (5s, 6 arom. C); 168.7, 170.2 (2s, 2 CˆO).
‡
CI-MS: 478(100, [ M ‡ 1] ), 266 (58), 213 (31). Anal. calc. for C26H23NO6S (477.54): C 65.39, H 4.85, N 2.93,
S 6.71; found: C 65.18, H 4.93, N 2.88, S 6.82.
With 7. After 24 h of heating, decomposition of starting materials was observed, and no [3 ‡ 4] cycloadduct
could be detected in the mixture.
5. Reaction of Adamantanethione with Azomethine Ylide 13. To the preheated soln. of 12a (373 mg,
1.1 mmol) in 2 ml of xylene (see 2,b) was added freshly prepared adamantanethione (166 mg, 1 mmol). After
heating for 4 h, no adamantanethione was detected by TLC; the solvent was evaporated i.v., and the residue was

Helvetica Chimica Acta Vol. 85 (2002)
2063
triturated with a small amount of MeOH. After storage in the refrigerator overnight, colorless crystals were
filtered and recrystallized from MeOH.
Dimethyl 3',4'-Diphenylspiro[adamantane-2,5'-[1,3]thiazolidine]-2',2'-dicarboxylate (16): Yield: 308mg
(82%). Colorless crystals. M.p. 150 1528 ([12]: 152 1548). IR (KBr): 700m, 748m, 1053m, 1207s, 1225vs, 1294s,
1
1498s, 1597s, 1747vs (CˆO), 1765vs (CˆO). H-NMR: 1.43 2.51 (m, 10 H); 3.55, 3.80 (2s, 2 MeO); 5.93 (s,
HÀC(2)); 6.32 7.58( m, 10 arom. H). 13C-NMR: 26.4, 26.8, 35.9, 37.2 (4d, 4 CH); 32.6, 33.2, 37.1, 38.1, 38.5 (5t, 5
CH2); 52.4, 53.2 (2q, 2 MeO); 67.3 (d, C(2)); 71.5 (s, C(5)); 83.5 (s, C(4)); 114.7, 118.6, 126.6, 127.2, 128.4, 128.6
(6d, 10 arom. CH); 143.0, 146.0 (2s, 2 arom. C); 168.3, 170.0 (2s, 2 CˆO).
6. Desulfurization of 1,3-Thiazolidines 14, 15 with Raney-Ni. To a soln. of 0.5 mmol of 14 or 15 in 3 ml of
CH2Cl2 was added Raney-Ni (ca. three-fold weight amount) suspended in MeOH. The mixture was stirred
magnetically at r.t. for 48h. Then, the mixture was filtered to remove Raney-Ni, and the black residue was
washed with 5 ml of CH2Cl2 (3Â). The org. solns. were combined, the solvents were removed i.v., and the solid
residues were crystallized from MeOH.
Dimethyl 1',4'-Diphenylspiro[9H-fluorene-9,3'-azetidine]-2',2'-dicarboxylate (17). Yield: 185 mg (78%).
Colorless prisms. M.p. 200 2018 (MeOH). IR (KBr): 694m, 752s, 1053m, 1140s, 1232vs, 1271vs, 1317s, 1450vs,
1
1495vs, 1604s, 1736vs (CˆO), 1753vs (CˆO). H-NMR: 3.14, 3.58(2 s, 2 MeO); 6.17 (s, HÀC(4')); 6.94 7.80
(m, 18arom. H). 13C-NMR: 51.7, 52.5 (2q, 2 MeO); 60.4 (s, C(2')); 69.8( d, C(4')); 82.5 (s, C(3')); 115.5, 119.2,
120.0, 120.6, 125.6, 125.7, 126.6, 127.1, 127.5, 127.8, 127.9, 128.8, 129.3 (13d, 18arom. CH); 137.1, 140.5, 141.0,
‡
142.6, 143.3, 148.2 (6s, 6 arom. C); 166.9, 168.7 (2s, 2 CˆO). CI-MS: 476 (55, [M ‡ 1] ), 255 (46), 224 (100), 222
(85). Anal. calc. for C31H25NO4 (475.55): C 78.30, H 5.30, N 2.95; found: C 77.98, H 5.07, N 2.94.
Dimethyl 1,3,3,4-Tetraphenylazetidine-2,2-dicarboxylate (18). Yield: 198mg (38%). Colorless crystals.
M.p. 154 1558 (MeOH/CH2Cl2). IR (KBr): 706s, 764m, 1057m, 1138m, 1267vs, 1448m, 1495vs, 1603s, 1738vs
(CˆO), 1751vs (CˆO). 1H-NMR: 2.99, 3.60 (2s, 2 MeO); 6.37 (s, HÀC(4)); 6.84 7.44 (m, 20 arom. H).
13C-NMR: 51.8, 52.3 (2q, 2 MeO); 62.7 (s, C(2)); 70.7 (d, C(4)); 86.0 (s, C(3)); 115.1, 120.5, 126.6, 127.2, 127.4,
127.6, 128.3, 128.5, 128.7, 129.1 (10d, 20 arom. CH); 137.9, 140.5, 142.0, 148.9 (4s, 4 arom. C); 168.1, 170.2 (2s, 2
‡
CˆO). CI-MS: 478(100, [ M ‡ 1] ), 222 (18). Anal. calc. for C31H27NO4 (477.56): C 77.97, H 5.70, N 2.93; found:
C 77.69, H 5.52, N 2.96.
7. Synthesis of N-Substituted 4,5-Dihydro-5-phenyl-1H-[1,2,3]triazole-4,4-dicarboxylates 12c and 12d.
General Procedure. Dimethyl benzylidenemalonate (2.20 g, 10 mmol) and 35 mmol of PhCH2N3 and BuN3
azide, resp., without solvent were placed in a round-bottom flask, and the mixture was heated to 508 (oil bath).
While heating during the day and keeping at r.t. at night, the reaction was continued for 30 d. Then, remaining
azide was removed by bulb-to-bulb distillation at 408/10À3 Torr. The residual, thick oil was purified by CC (SiO2)
with hexane and increasing amounts of CH2Cl2 as the eluant. Pure products were isolated as thick oils, which did
not crystallize even after storage in the refrigerator for several days.
Dimethyl 1-Butyl-4,5-dihydro-5-phenyl-1H-[1,2,3]triazole-4,4-dicarboxylate (12c). Yield: 2.25 g (71%).
Colorless oil. IR (CHCl3): 1124m, 1171m, 1286vs, 1437s, 1456m, 1741vs (CˆO), 2875w, 2958s, 3008m (br.).
1H-NMR: 0.89 (t, Me); 1.10 1.85 (m, 2 CH2); 3.20, 3.90 (2s, MeO); 3.70 (t, CH2N); 5.35 (s, HÀC(5)); 7.10 7.45
(m, 5 arom. H). 13C-NMR: 13.6 (q, Me); 19.9, 29.9, 47.9 (3t, 3 CH2); 52.4, 53.8(2 q, 2 MeO); 66.0 (d, C(5)); 94.9
(s, C(4)); 128.3, 129.0, 129.3 (3d, 5 arom. CH); 133.9 (s, 1 arom. C); 165.5, 167.0 (2s, 2 CˆO). CI-MS: 320 (100,
‡
[M ‡ 1] ), 262 (10), 162 (9). Anal. calc. for C16H21N3O4 (319.36): C 60.18, H 6.63, N 13.16; found: C 60.18,
H 6.45, N 13.31.
Dimethyl 1-Benzyl-4,5-dihydro-5-phenyl-1H-[1,2,3]triazole-4,4-dicarboxylate (12d). Yield: 2.40 g (67%).
1
Colorless oil. IR (CHCl3): 1130s, 1285vs, 1440s, 1456s, 1741vs (CˆO), 2956m, 3014s. H-NMR: 3.16, 3.76 (2s,
2 MeO); 4.24, 5.32 (AB, J ˆ 15.0, CH2); 5.05 (s, HÀC(5)); 6.95 7.80 (m, 10 arom. H). 13C-NMR: 52.0 (t, CH2);
52.5, 53.8(2 q, 2 MeO); 64.9 (d, C(5)); 95.0 (q, C(4)); 128.4, 128.5, 128.7, 129.0, 129.1, 129.3 (6d, 10 arom. CH);
‡
133.2, 134.7 (2s, 2 arom. C); 165.2, 166.6 (2s, 2 CˆO). CI-MS: 354 (100, [M ‡ 1] ), 296 (8), 268 (7). Anal. calc.
for C19H23N3O4 (357.41): C 63.85, H 6.49, N 11.76; found: C 63.15, H 5.42, N 11.76.
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Received April 18, 2002