Synthesis of some novel thioxanthenone-fused azacrown ethers, and their use as new catalysts in the efficient, mild, and regioselective conversion of epoxides to β-hydroxy thiocyanates with ammonium thiocyanate

Article abstract of DOI:10.1002/hlca.200790139

The regioselective ring-opening reactions of some epoxides with ammonium thiocyanate in the presence of a series of new 9H-thioxanthen-9-one-fused azacrown ethers, i.e., 7-11 (Scheme 1), and also of dibenzo[18]crown-6 (12), Kryptofix 22 (13), and benzo[15]crown-5 (14) were studied (Tables 1 and 2). The epoxides were subjected to cleavage by NH₄SCN in the presence of these catalysts under mild conditions in various aprotic solvents. Reagents and conditions were identified for the synthesis of individual β-hydroxy thiocyanates in high yield and with more than 90% regioselectivity. The results can be discussed in terms of a four-step mechanism (Scheme 2): 1) formation of a complex between catalyst and NH₄SCN, 2) release of SCN^- from the complex, 3) reaction of the released SCN^- at the sterically less hindered site of the epoxide, and 4) regeneration of the catalyst. The major advantages of this method are the high regioselectivity, the simple regeneration of the catalyst, the reuse of it through several cycles without a decrease of activity, and the ease of workup of the reaction mixtures.

Full text of DOI:10.1002/hlca.200790139

Helvetica Chimica Acta – Vol. 90 (2007)
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Synthesis of Some Novel Thioxanthenone-Fused Azacrown Ethers, and Their
Use as New Catalysts in the Efficient, Mild, and Regioselective Conversion of
Epoxides to b-Hydroxy Thiocyanates with Ammonium Thiocyanate
by Hashem Sharghi*, Alireza Salimi Beni, and Reza Khalifeh
Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, I. R. Iran
(phone: 00987112284822; fax: 00987112280926; e-mail: shashem@chem.susc.ac.ir)
The regioselective ring-opening reactions of some epoxides with ammonium thiocyanate in the
presence of a series of new 9H-thioxanthen-9-one-fused azacrown ethers, i.e., 7 – 11 (Scheme 1), and also
of dibenzo[18]crown-6 (12), Kryptofixꢀ 22 (13), and benzo[15]crown-5 (14) were studied (Tables 1 and
2). The epoxides were subjected to cleavage by NH4SCN in the presence of these catalysts under mild
conditions in various aprotic solvents. Reagents and conditions were identified for the synthesis of
individual b-hydroxy thiocyanates in high yield and with more than 90% regioselectivity. The results can
be discussed in terms of a four-step mechanism (Scheme 2): 1) formation of a complex between catalyst
and NH4SCN, 2) release of SCNꢀ from the complex, 3) reaction of the released SCNꢀ at the sterically less
hindered site of the epoxide, and 4) regeneration of the catalyst. The major advantages of this method are
the high regioselectivity, the simple regeneration of the catalyst, the reuse of it through several cycles
without a decrease of activity, and the ease of workup of the reaction mixtures.
Introduction. – Epoxides are one of the most versatile intermediates in organic
synthesis, and a large variety of reagents are known for the ring opening of these
compounds [1]. Their electrophilic reaction with different nucleophiles has been a
permanent subject in organic synthesis [2 – 7]. Among these nucleophiles, the reaction
of the thiocyanate ion with epoxides, in the absence or in the presence of a catalyst, is a
widely studied and suitable method for the preparation of thiiranes [8 – 15]. The
formation of thiiranes from the reaction of epoxides and thiocyanate ions has been
proposed to occur through the intermediacy of the corresponding b-hydroxy
thiocyanate, but this intermediate has not been isolated due to its rapid conversion
to the corresponding thiirane [13 – 17]. There are two methods reported in the
literature for the synthesis of b-hydroxy thiocyanates. In one method, thiocyanohydrins
are prepared by opening of a cyclic sulfate with NH4SCN to form the corresponding b-
sulfate, which is then hydrolyzed to the thiocyanohydrines. A second method employs
the addition of thiocyanic acid, generated in situ at low temperature, to the epoxide
[18 – 21]. It has been reported for these syntheses that the presence of some
hydroquinone (¼ benzene-1,4-diol) or DDQ (¼4,5-dichloro-3,6-dioxocyclohexa-1,4-
diene-1,2-dicarbonitrile) is required to stabilize the produced b-hydroxy thiocyanate
and to inhibit its conversion to thiirane [16][22]. Although the reagents such as
Ti(OiPr)4 [23], Ph3P · (SCN)2 [24], TiCl3 (or ZnCl2) [25], and [Pd(PPh3)4] [26] are
ꢁ 2007 Verlag Helvetica Chimica Acta AG, Zürich

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useful, they are limited to specific oxiranes and are not applicable as versatile reagents
in the preparation of b-hydroxy thiocyanates [27].
In conjunction with the ongoing work in our laboratory on the synthesis and
complex formation of macrocyclic compounds with different molecules [28 – 33], we
found that thioxanthenone-fused crown ethers efficiently catalyzed the addition of
ammonium thiocyanate to epoxides to form b-hydroxy thiocyanates. The four new
crown ethers 7 – 10 as well as dibenzo[18]crown-6 (12), Kryptofixꢀ 22 (13), and
benzo[15]crown-5 (14) were selected as catalysts for the ring opening of epoxides by
NH4SCN.
Results and Discussion. – 1. Preparation of Catalyst. Although macrocyclic amides
are originally regarded as intermediates to prepare azacrown ligands, only a few
procedures have been developed for their preparations. Among these, carboxylic acid
derivatives, such as malonic and a,w-dicarboxylic acid esters [34], labile diacyl
dichlorides [35][36], and bis(a-chloroamide) compounds [37 – 39], were allowed to
react with various diamides under high dilution or for long reaction periods.
We have previously shown that some azacrown ethers can be prepared by a simple
and convenient procedure [40]. We reported a new efficient synthesis of macrocyclic
diamides under mild conditions. No high-dilution technique or fast-addition method
was required in this new method. We now applied this procedure to the synthesis of
thioxanthenone-fused azacrown compounds 7 and 8 (Scheme 1). As shown in
Scheme 1, thiosalicylic acid (1) was treated with pyrocatechol (2) in concentrated
sulfuric acid [41 – 44] to give yellow powdery 2,3-dihydroxy-9H-thioxanthen-9-one (3)
and 1,2-dihydroxy-9H-thioxanthen-9-one (4) in 70% yield (9 :1). The diesters 5 and 6
were obtained by reaction of the corresponding dihydroxythioxanthenones with ethyl
bromoacetate in 70% and 60% yield, respectively.
The cyclization reaction of diesters 5 and 6 with diethylene triamine (¼ N1-(2-
aminoethyl)ethane-1,2-diamine) was performed, without using a high-dilution techni-
que or fast-addition method, at 508 in EtOH to give the corresponding thioxanthenone-
fused crown ether 7 and 8 in 70 and 60% yield, respectively. The compounds 9 – 11 were
obtained by reaction of the 7 with the corresponding phenols 8a – c in the presence of
paraformaldehyde on silica gel under solvent-free conditions in yields of 50 – 65%. The
commercially available and established crown ethers 12 – 14 were also used as catalysts
in the thiocyanation of epoxides.
2. Thiocyanation of Epoxides. The results of the reaction of ꢂstyrene oxideꢃ (¼2-
phenyloxirane) with thiocyanate ions in the presence of the above catalysts are
summarized in Table 1. In each case, cleavage of the epoxide ring occurred, and upon

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Scheme 1
workup, the corresponding thiocyanohydrin was obtained. The catalyst was easily
recovered and could be reused several times. As shown in Table 1, yields of
thiocyanation with this new methodology were quite good. Catalysts 9 and 10 in

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Helvetica Chimica Acta – Vol. 90 (2007)
MeCN were the most effective, and the reactions were completed within 25 and 40 min,
respectively (Table 1, Entries 3 and 4). In the presence of the catalysts 7, 8, and 12 – 14,
the reaction time for thiocyanation at 808 was in the range of 40 – 90 min (Entries 1, 2,
and 6 – 8). However, the reaction of styrene oxide with an excess of ammonium
thiocyanate in the absence of catalyst afforded the corresponding thiirane in 35% yield
when the reaction mixture was refluxed for ca. 3 h (Entry 9). The ring opening of
styrene oxide in the presence of macrocycle 9 in various solvents revealed that the
reaction proceeded very cleanly in MeCN, while those performed in DMF and CH2Cl2
led to a lower yield of the thiocyanohydrin (Table 1).
Table 1. Ring Opening of ꢀStyrene Oxideꢁ (¼ 2-Phenyloxirane; 1 mmol) with NH4SCN (1 mmol) in the
Presence of Various Macrocyclic Compounds in Different Solvents (3 ml) under Reflux Conditions
Entry
Catalyst [0.01 mol-%]
Solvent
Time [min]
Yield [%]a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
7
8
9
10
11
12
13
14
–
9
9
9
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
45
40
25
40
90
85
60
90
190b)
120
100
100
80
87
83
95
90
55
70
65
65
c
MeCN
DMF
)
< 15
40
20
40
< 20
30
acetone
EtOH/H2O (2 : 1)
THF
CH2Cl2
1,4-dioxane
9
9
100
65
a) Determined by GC. b) In the presence of excess of NH4SCN. c) The corresponding thiirane was
obtained in 35% yield.
Some further procedures for the conversion of epoxides into the corresponding
thiocyanohydrins are given in Table 2 (Entries 1 – 5). However, when epoxides were
allowed to react in the presence of our catalysts, the yield and the regioselectivity were
higher under all of the conditions studied. Generally, the optimum amount of catalyst
was 0.01 mmol for 1 mmol of epoxide and 1 mmol of NH4SCN. However, other factors
can exert a controlling influence, such as 1) steric hindrance of the involved epoxide, 2)
the nature of the applied solvent, and 3) electron-donating or electron-withdrawing
groups bonded to the epoxide. Each one can have a pronounced effect on the observed
ratio of thiocyanohydrin isomers and the overall yield. The reaction exhibited the
expected anti-stereoselectivity, as shown for cyclohexene oxide (¼ 7-oxabicyclo[4.1.0]-
heptane) (Table 2, Entry 16), in which only the trans-isomer was detected. The anti-
Markovnikov-type [39] regioselectivity was generally observed in these reactions,

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except for the reactions of ꢂstyrene oxideꢃ (Table 2, Entry 7). The reactions of other
epoxides were found to be highly regioselective, and only one isomer was obtained. In
these reactions, 5 – 8% of the corresponding thiiranes were also formed, which could
easily be isolated by column chromatography.
The regiochemical mode of epoxide cleavage by ammonium thiocyanate in the
presence of a macrocycle catalyst can be viewed as occurring via nucleophilic attack by
the thiocyanate ion on the sterically less hindered C-atom of the epoxide. This
mechanism closely resembles the SN2 model for an aliphatic nucleophilic substitution.
On the basis of our previous study on macrocycle diamides and other works on the
complexation of crown ethers with elemental halogens, alkaline-metal ions, ammonium
cation, and alkylamines [28 – 33], conversion of epoxide to b-hydroxy thiocyanate
occurs according to the following four-step mechanism (Scheme 2): The first step
involves the formation of a 1:1 molecular complex between the macrocycle and
NH4SCN, in which the thiocyanate ion (SCNꢀ) exists as a contact ion pair. In the
second step, this complex is decomposed to release SCNꢀ into the solution, thus
producing SCNꢀ as a nucleophilic species in the presence of a suitable macrocycle. In
the third step, the released SCNꢀ induces the ring-opening reaction of the epoxides.
Finally, the catalyst is regenerated in the fourth step. These steps occur continuously
until all of the epoxide and ammonium thiocyanate are consumed, and after workup,
the catalyst can be recovered easily.
Scheme 2
The variation in yield and rate of the epoxide ring opening by SCNꢀ in the presence
of the different catalysts 7 – 14 can be rationalized in terms of the suggested mechanism.
The macrocycles 9 and 10 are the most active catalysts in these reactions. According to
the mechanism, in the case of both macrocycles 9 and 10, the complexation of NH4SCN
and, hence, liberation of SCNꢀ occurred much faster than in the case of other catalysts.
In support of this mechanism, the interaction of catalyst 9 with NH4SCN was
established by the UV/VIS spectra (MeCN) of catalyst 9 of NH4SCN and of catalyst 9
in the presence of NH4SCN (Fig. 1). The azacrown ether 9 possesses a chromophor, i.e.,
the thioxanthenone backbone, that exhibits almost no absorption above 400 nm,
whereas NH4SCN shows a weak broad absorption band at ca. 450 nm which may be

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Fig. 1. UV/VIS Absorption Spectra of a) Catalyst 9, (0.01 mol), b) NH4SCN (1.0 mol), and c) NH4SCN
(1.0 mol) in the presence of catalyst 9 (0.01 mol), all in MeCN at room temperature
assigned to an n,p* transition of the SCNꢀ ions still interfering with their NHþ4
counterions via H-bonding. It seems that this interference vanishes completely in the
presence of azacrown ether 9 due to the capture of the NHþ4 ions by complex formation
with 9. As a result, the n,p* transition of SCNꢀ is strongly enhanced (hyperchromic
effect) and slightly shifted to longer wavelengths (bathochromic effect). Another
explanation would be the formation of a charge-transfer complex between the ꢂnakedꢃ
thiocyanate ions and the thioxanthenone backbone, whose strong absorption would be
seen at ca. 470 nm. This second possibility was excluded by the UV/VIS spectrum
(MeCN) of NH4SCN in the presence of azacrown ether 13 devoid of an additional
aromatic chromophor (Fig. 2): this spectrum exhibits the same hyperchromic and
bathochromic effect on the n,p* transition of SCNꢀ.
In conclusion, we found that suitable macrocyclic compounds can catalyze the
regioselective ring opening of epoxides by ammonium thiocyanate under mild reaction
conditions. Especially noteworthy are the ease of catalyst regeneration and reuse, the
compatibility of the reaction conditions with a variety of sensitive functional groups, as
well as the convenience of the procedure, which make this synthetic technique highly
useful.
Experimental Part
General. Chemical materials were either prepared in our laboratories or were purchased from Fluka,
Aldrich, and Merck. The 2-hydroxy-9H-thioxanthen-9-one and 1-fluoro-4-hydroxy-9H-thioxanthen-9-
one were synthesized according to [41 – 44].
TLC: silica gel PolyGram SILG/UV 254 plates. Column chromatography (CC): silica gel 60 (70 – 230
mesh) in short glass columns (2 – 3 cm diameter); 15 – 30 g of silica gel per 1 g of crude mixture. M.p.:
Büchi 535 circulating-oil melting-point apparatus; open capillary tubes. IRSpectra: Shimadzu FT-IR-

Helvetica Chimica Acta – Vol. 90 (2007)
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Fig. 2. UV/VIS Absorption Spectra of a) NH4SCN (0.01 mol) and b) NH4SCN (1.0 mol) in the presence
of catalyst 13 (0.01 mol), both in MeCN, at room temperature
8300 spectrophotometer; in cmꢀ1. NMRSpectra: Bruker Avance-DPX-250 spectrometer; 1H at 250 and
13C at 62.9 MHz; in pure deuterated solvents with SiMe4 as an internal standard; d in ppm, J in Hz. Mass
spectra: Shimadzu GCMS-QP-1000-EX instruments at 70 or 20 eV; in m/z (rel. %).
2,3-Dihydroxy- and 1,2-Dihydroxy-9H-thioxanthen-9-one (3 and 4, resp.). Thiosalicylic acid (¼2-
mercaptobenzoic acid; 1.6 g, 0.01 mol) was slowly added to cold conc. (98%) sulfuric acid (15 ml), and
the mixture was stirred for 5 min to insure thorough mixing. Pyrocatechol (¼ benzene-1,2-diol; 3.0 g,
0.027 mol) was added slowly to the stirred mixture within 30 min. After the addition, the mixture was
stirred at r.t. for 18 h and then at 808 for 1 h. (red ! dark red mixture on heating). The mixture was then
cooled to r.t. and poured slowly into ice-water (300 ml). The resulting yellow precipitate was filtered,
washed with H2O (3 ꢁ 50 ml), sat. aq. NaHCO3 soln. and H2O (removal of alkali), and dried at r.t.
overnight: 1.7 g (70%) of 3/4 (9 :1). The thioxanthones were separated by CC.
1
Data of 4. M.p. 196 – 1988. IR(KBr): 3250 (br.), 1630 s, 1580s, 1480s, 1450s, 1350s, 1220s. H-NMR
(CDCl3, 250 MHz): 14.02 (s, 1 H); 8.50 (d, J ¼ 8.0, 1 H); 7.36 – 7.58 (m, 3 H); 7.22 (d, J ¼ 8.5, 1 H); 6.93
(d, J ¼ 8.5, 1 H); 5.72 (s, 1 H). 13C-NMR(CDCl 3, 62.9 MHz): 182.5; 150.0; 141.2; 131.7; 129.0; 128.0;
127.0; 126.0; 124.8; 124.5; 119.8; 114.0; 113.0. MS: 244 (100, Mþ), 187 (18), 115 (16). Anal. calc. for
C13H8O3S (244.26): C 63.92, H 3.30; found: C 63.84, H 3.24.
Data of 3. M.p. > 3008. IR(KBr): 3490 (br.), 1600 s, 1580s, 1550s, 1510s, 1438s, 1276s. 1H-NMR
(D6)DMSO, 250 MHz): 10.50 (s, 1 H); 9.97 (s, 1 H); 8.42 (d, J ¼ 7.9, 1 H); 7.87 (s, 1 H); 7.66 – 7.87 (m,
2 H); 7.52 (t, J ¼ 6.7, 1 H); 7.05 (s, 1 H). 13C-NMR(D 6)DMSO, 62.9 MHz): 177.7; 152.3; 146.2; 136.8;
132.3; 129.1; 128.9; 128.3; 126.6; 126.5; 121.7; 114.3; 111.1. MS: 244 (100, Mþ), 216 (22), 187 (17), 115
(20). Anal. calc. for C13H8O3S (244.26): C 63.92, H 3.30; found: C 63.79, H 3.26.
Diethyl 2,2’-[(9-Oxo-9H-thioxanthene-2,3-diyl)bis(oxy)]bis[acetate] (5). To the mixture of K2CO3
(5 g) in dried acetone (400 ml) was added 3 (2.5 g, 0.01 mol) and ethyl bromoacetate (4 ml, 0.024 mol).
The resulting mixture was stirred at r.t. for 24 h. The mixture was filtered, the solvent evaporated, and the
yellow solid recrystallized from EtOH: 5 (2.6 g, 70%). Yellow solid. M.p. 129 – 1308. IR(KBr): 1755 s,
1726s, 1631s, 1595s, 1504s, 1436s, 1145s. 1H-NMR(CDCl 3, 250 MHz): 8.53 (d, J ¼ 8.0, 1 H); 7.98 (s, 1 H);
7.36 – 7.56 (m, 3 H); 6.87 (s, 1 H); 4.82 (s, 4 H); 4.24 – 4.32 (m, 4 H); 1.19 – 1.35 (m, 6 H). 13C-NMR
(CDCl3, 62.9 MHz): 178.4; 168.0; 167.8; 151.7; 147.1; 136.9; 131.9; 131.7; 129.6; 128.4; 126.2; 125.8; 123.9;

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Helvetica Chimica Acta – Vol. 90 (2007)
112.6; 109.6; 66.3; 65.8; 61.6; 61.5; 14.1. MS: 416 (11.8, Mþ), 329 (3.4), 287 (13.4), 255 (4.9), 204 (10), 149
(10) 69 (100). Anal. calc. for C21H20O7S (416.44): C 60.57, H 4.84; found: C 60.68, H 4.77.
Diethyl 2,2’-[(9-Oxo-9H-thioxanthene-1,2-diyl)bis(oxy)]bis[acetate] (6). As described for 5, with
K2CO3 (5 g), acetone (200 ml), 4 (2.5 g, 0.01 mol), and ethyl bromoacetate (4 ml, 0.024 mol), for 24 h
under reflux. The yellow solid was subjected to CC (silica gel, CHCl3/hexane): 6 (2.1 g, 60%). Yellow
solid. M.p. 104 – 1058. IR(KBr): 1750 s, 1723s, 1630s, 1590s, 1504s, 1430s, 1145s. 1H-NMR(CDCl
,
3
250 MHz): 8.31 (d, J ¼ 7.6, 1 H); 7.32 – 7.45 (m, 5 H); 4.79 (s, 2 H); 4.68 (s, 2 H); 4.27 (q, J ¼ 7.1, 2 H); 4.16
(q, J ¼ 7.1, 2 H); 1.25 (t, J ¼ 7.1, 3 H); 1.19 (t, J ¼ 7.1, 3 H ) . 13C-NMR(CDCl 3, 62.9 MHz): 180.4; 169.1;
168.7; 150.0; 149.9; 135.7; 131.8; 130.9; 129.6; 126.2; 125.1; 122.2; 121.7; 70.2; 67.5; 61.3; 60.9; 14.2; 14.1.
MS: 416 (11.8, Mþ), 329 (3.4), 287 (13.4), 255 (4.9), 204 (10), 149 (10) 69 (100). Anal. calc. for C21H20O7S
(416.44): C 60.57, H 4.84; found: C 60.65, H 4.73.
5,6,7,8,9,10-Hexahydro-2H,20H-thioxantheno[2,3-b] [1,4,7,10,13]dioxatriazacyclopentadecine-
3,11,20(4H,12H)-trione (7). To a soln. of 5 (1.5 g, 0.0036 mol) in EtOH (400 ml) was added N1-(2-
aminoethyl)ethane-1,2-diamine (0.4 ml 0.0038 mol), and the mixture was left overnight at 508. After this
time, the precipitate was collected by filtration: 7 (1.1 g, 70%). M.p. > 3008. IR(KBr): 3396 (br.), 1690 s,
1
1595s, 1542s, 1504s, 1259s, 1143s, 750s. H-NMR((D )DMSO, 250 MHz): 8.43 (d, J ¼ 7.6, 1 H); 7.87 (s,
6
1 H); 7.69 – 7.88 (m, 4 H); 7.55 (t, J ¼ 7.0, 1 H); 7.46 (s, 1 H); 4.65 (s, 4 H); 2.73 (s, 3 H); 2.48 (s, 4 H).
13C-NMR(CDCl 3, 62.9 MHz): 177.7; 166.2; 165.9; 152.7; 146.2; 136.4; 129.8; 128.0; 126.8; 117.8; 112.1;
67.8; 50.7; 35.1. MS: 428 (0.8, [M þ 1]þ), 427 (5.4, Mþ), 384 (4.2), 359 (28.7), 285 (49.0), 257 (38.7), 228
(16.1), 171 (25.7%), 56 (100). Anal. calc. for C21H21N3O5S (427.47): C 59.00, H 4.95; found: C 59.36, H
4.86.
5,6,7,8,9,10-Hexahydro-2H,21H-thioxantheno[1,2-b] [1,4,7,10,13]dioxatriazacyclopentadecine-
3,11,21(4H,12H)-trione (8). As described for 7, with 6 (1.5 g, 0.0036 mol), EtOH (200 ml), and N1-(2-
aminoethyl)ethane-1,2-diamine (0.4 ml, 0.0038 mol) for 48 h. The mixture was concentrated and the
yellow solid subjected to CC (silica gel, EtOH/AcOEt): 8 (0.9 g, 60%). Yellow solid. M.p. 232 – 2348. IR
(KBr): 3393 (br.), 1685s, 1592s, 1540s, 1514s, 1250s, 1133s, 752s. 1H-NMR(CDCl 3, 250 MHz): 8.44 (d, J ¼
8.0, 1 H); 7.69 (s, 2 H); 7.44 – 7.58 (m, 3 H); 7.38 (d, J ¼ 8.9, 1 H); 7.22 (d, J ¼ 8.9, 1 H); 4.61 (s, 2 H); 4.50
(s, 2 H); 3.49 – 3.56 (m, 2 H); 3.41 – 3.47 (m, 2 H); 2.86 – 2.90 (m, 4 H); 1.64 (s, 1 H). 13C-NMR(CDCl 3,
62.9 MHz): 168.7; 166.4; 157.0; 148.5; 142.0; 136.0; 132.2; 130.0; 129.7; 126.4; 125.4; 122.9; 117.7; 72.1;
67.5; 46.4; 45.7; 37.8; 37.2. MS: 427 (25.0, Mþ), 384 (4.2), 359 (26.9), 285 (51.3), 257 (32.3), 228 (23.1), 171
(35.7), 56 (100). Anal. calc. for C21H21N3O5S (427.47): C 59.00, H 4.95; found: C 59.38, H 4.87.
Thioxanthenone-FusedAzacrown Ethers 9 – 11: General Procedure. Azacrown ether 7 (1 mmol), a
phenol 8 (2 mmol), paraformaldehyde (2 mmol), and silica gel (1 g) were thoroughly mixed. The
resulting fine powder was transferred to a round-bottom flask and stirred in an oil bath at 1208 for 2 h.
After cooling, CHCl3 (3 ꢁ 25 ml) was added, and the silica gel was removed by filtration. Evaporation of
the solvent gave the crude product in 50 – 70% yield, which was purified by CC (EtOH/AcOEt).
7-[5-(tert-Butyl)-2-hydroxybenzyl]-5,6,7,8,9,10-hexahydro-2H,20H-thioxantheno[2,3-b] [1,4,7,
10,13]dioxatriazacyclopentadecine-3,11,20(4H,12H)-trione (9): M.p. 248 – 2508. IR(KBr): 3371 (br.),
1
2956s, 1670s, 1596s, 1437s, 1209s, 825s, 750s. H-NMR(CDCl 3, 250 MHz): 8.46 (d, J ¼ 6.9, 1 H); 7.94 (s,
1 H); 7.85 (s, 1 H); 7.77 (s, 1 H); 7.39 – 7.46 (m, 3 H); 7.24 (dd, 3J ¼ 8.4, 4J ¼ 2.4, 1 H); 7.20 (s, 1 H); 7.00 (d,
J ¼ 8.4, 1 H); 6.59 (s, 1 H); 4.68 (s, 2 H); 4.14 (s, 2 H); 3.80 (s, 2 H); 3.48 (s, 4 H); 2.77 (s, 4 H); 1.30 (s,
12 H). 13C-NMR(CDCl 3, 62.9 MHz): 177.3; 166.2; 165.9; 154.7; 150.9; 147.3; 146.2; 136.4; 132.2; 131.9;
131.4; 130.2; 128.8; 127.7; 127.3; 126.6; 126.3; 122.8; 116.5; 112.0; 67.5; 52.1; 49.3; 36.8; 32.0; 29.7. MS: 427
(13.4, [M ꢀ 163]þ), 359 (45.7), 285 (49.6), 147 (100), 73 (37). Anal. calc. for C32H32N3O6S (589.70): C
65.18, H 5.98; found: C 65.46, H 5.86.
5,6,7,8,9,10-Hexahydro-7-(2-hydroxy-5-methylbenzyl)-2H,20H-thioxantheno[2,3-b][1,4,7,10,13]di-
oxatriazacyclopentadecine-3,11,20(4H,12H)-trione (10): M.p. 256 – 2588. IR(KBr): 3382 (br.), 2950 s,
1662s, 1588s, 1430s, 1215s, 829s, 740s. 1H-NMR(CDCl 3, 250 MHz): 9.19 (s, 1 H); 8.41 (d, J ¼ 7.9, 1 H); 7.88
(s, 1 H); 7.51 – 7.84 (m, 5 H); 7.46 (s, 1 H); 6.97 (s, 1 H); 6.75 (d, J ¼ 8.0, 1 H); 6.57 (d, J ¼ 8.0, 1 H); 4.57 (s,
4 H); 3.77 (s, 2 H); 2.63 (s, 8 H); 1.99 (s, 3 H). 13C-NMR(CDCl 3, 62.9 MHz): 177.4; 166.3; 165.9; 154.7;
150.9; 146.2; 136.5; 132.4; 132.1; 131.4; 130.1; 128.8; 127.7; 127.2; 126.5; 122.6; 116.8; 112.0; 67.6; 52.3;
49.3; 19.7. MS: 359 (21.4, [M ꢀ 188]þ), 285 (33.9), 284 (16.1), 257 (26.8), 171 (16.1), 139 (12.5), 56 (100).
Anal. calc. for C29H29N3O6S (547.62): C 63.60, H 5.34; found: C 65.34, H 5.46.

Helvetica Chimica Acta – Vol. 90 (2007)
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7-(5-Bromo-2-hydroxybenzyl)-5,6,7,8,9,10-hexahydro-2H,20H-thioxantheno[2,3-b][1,4,7,10,13]diox-
atriazacyclopentadecine-3,11,20(4H,12H)-trione (11): M.p. 252 – 2548. IR(KBr), 3382 (br.), 2950 s, 1662s,
1588s, 1430s, 1215s, 829s, 740s. 1H-NMR(CDCl 3, 250 MHz): 9.78 (s, 1 H); 8.43 (d, J ¼ 7.9, 1 H); 7.69 – 7.81
(m, 4 H); 7.55 (t, J ¼ 7.5, 1 H); 7.48 (s, 1 H); 7.37 (s, 1 H); 7.07 (dd, 3J ¼ 8.5, 4J ¼ 2.5, 1 H); 6.65 (d, J ¼ 8.6,
1 H); 4.59 (s, 4 H); 3.51 (s, 2 H); 2.65 (s, 8 H). 13C-NMR(CDCl 3, 62.9 MHz): 177.3; 166.3; 165.9; 154.7;
151.0; 146.2; 136.4; 132.3; 132.0; 131.4; 130.1; 128.8; 127.7; 127.3; 126.6; 126.3; 122.6; 116.9; 111.4; 109.9;
109.3; 67.5; 52.2; 49.4; 35.2. MS: 359 (27.5, [M ꢀ 253]þ), 285 (30.7), 284 (20.2), 257 (24.6), 171 (18.9), 139
(10.3), 56 (100). Anal. calc. for C28H26BrN3O6S (612.49): C 54.91, H 4.28; found: C 54.67, H 4.12.
Synthesis of Some New Epoxides: General Procedure. To the mixture of K2CO3 in dried acetone was
added the corresponding phenol and epibromohydrine. The resulting mixture was stirred under reflux for
48 h (TLC monitoring). The mixture was filtered, the solvent evaporated and the solid subjected to CC
(silica gel, hexane, then CHCl3 or AcOEt): epoxide (see Table 2) as a yellow or white solid.
2-(Oxiran-2-ylmethoxy)-9H-thioxanthen-9-one: M.p. 158 – 1598. IR(KBr): 1639 s, 1595s, 1437s, 1433s,
1230s, 1155s, 1024s, 740s. 1H-NMR(CDCl 3, 250 MHz): 8.55 (d, J ¼ 7.9, 1 H); 7.99 (s, 1 H); 7.51 – 7.54 (m,
1 H); 7.40 – 7.45 (m, 3 H); 7.21 – 7.26 (m, 1 H); 4.33 – 4.37 (m, 1 H); 3.94 – 4.00 (m, 1 H); 3.33 – 3.37 (m,
1 H); 2.86 – 2.89 (m, 1 H); 2.52 – 2.75 (m, 1 H). 13C-NMR(CDCl 3, 62.9 MHz): 180.0; 157.2; 137.4; 132.1;
130.2; 129.9; 127.5; 126.1; 125.9; 123.0; 111.1; 69.1; 49.9; 44.6. MS: 285 (2.2, [M þ 1]þ), 284 (20.7, Mþ), 228
(7.4), 227 (3.3), 171 (9.0), 149 (15.1), 129 (7.2), 73 (31.1). Anal. calc. for C16H12O3S (284.33): C 67.59, H
4.25; found: C 67.26, H 4.43.
1-Fluoro-4-(oxiran-2-ylmethoxy)-9H-thioxanthen-9-one: M.p. 155 – 1568. IR(KBr): 1641 s, 1596s,
1454s, 1311s, 1253s, 1053s, 744s. 1H-NMR(CDCl 3, 250 MHz): 8.49 (d, J ¼ 7.8, 1 H); 7.44 – 7.60 (m, 3 H);
7.00 – 7.11 (m, 2 H); 4.42 – 4.48 (m, 1 H); 4.05 – 4.12 (m, 1 H); 3.42 – 3.45 (m, 1 H); 2.95 – 2.99 (m, 1 H);
2.84 – 2.87 (m, 1 H). 13C-NMR(CDCl 3, 62.9 MHz): 159.8; 155.6; 148.5; 131.7; 129.7; 128.9; 126.1; 125.6;
114.4; 114.2; 112.7; 112.4; 70.0; 49.5; 44.0. MS: 303 (3.2, [M þ 1]þ), 302 (46.3, Mþ), 246 (19.4), 245 (21.9),
218 (5.5), 217 (6.0), 189 (25.0), 157 (7.8), 57 (100). Anal. calc. for C16H11FO3S (302.32): C 63.57, H 3.67;
found: C 63.05, H 3.37.
2-[(Naphthalen-1-yloxy)methyl]oxirane [45][46]: 1H-NMR(CDCl 3, 250 MHz): 8.52 (d, J ¼ 9.5,
1 H); 7.89 – 7.93 (m, 1 H); 7.55 – 7.63 (m, 3 H); 7.43 (t, J ¼ 7.7, 1 H); 6.72 (d, J ¼ 7.5, 1 H); 4.20 – 4.26 (m,
1 H); 3.86 – 3.93 (m, 1 H); 3.37 – 3.38 (m, 1 H); 2.82 – 2.86 (m, 1 H); 2.71 – 2.74 (m, 1 H). 13C-NMR
(CDCl3, 62.9 MHz): 154.4; 134.8; 127.7; 126.7; 126.1; 125.8; 125.5; 122.7; 121.3; 105.2; 69.0; 50.2; 44.3.
2-[(Naphthalen-2-yloxy)methyl]oxirane [45][46]: M.p. 69 – 718 ([45]: 68 – 708). 1H-NMR(CDCl
,
3
250 MHz): 7.60 – 7.68 (m, 2 H); 7.24 – 7.34 (m, 3 H); 7.02 – 7.11 (m, 2 H); 4.19 – 4.24 (m, 1 H); 3.90 – 3.97
(m, 1 H); 3.29 – 3.32 (m, 1 H); 2.79 – 2.83 (m, 1 H); 2.67 – 2.70 (m, 1 H). 13C-NMR(CDCl 3, 62.9 MHz):
155.9; 133.9; 129.0; 128.7; 127.2; 126.3; 125.9; 123.4; 118.3; 106.4; 68.2; 49.6; 44.2.
Conversion of Epoxides to b-Hydroxy Thiocyanates Using a Thioxanthenone Crown Ether as
Catalyst: General Procedure. To a mixture of epoxide (10 mmol) and NH4SCN (10 mmol, 0.76 g) in
MeCN (30 ml) was added a catalyst (0.1 mmol), and the mixture was stirred under reflux conditions for
35 – 90 min. The reaction was monitored by TLC or GC. After completion of the reaction, the mixture
was filtered, the solvent evaporated, and the crude product subjected to CC (silica gel, hexane, then CCl4/
CH2Cl2 1:1): b-hydroxy thiocyanate (Table 2) as a pale yellow liquid or solid. Selected spectral data for b-
hydroxy thiocyanates are given in the following [16][24][27].
2-Hydroxy-2-phenylethyl Thiocyanate: IR(neat): 2160 s (SCN). 1H-NMR(CDCl 3, 250 MHz): 7.25 –
7.33 (m, 5 H); 5.01 (dd, J ¼ 4.3, 1 H); 3.14 – 3.31 (m, 2 H); 2.4 – 2.9 (br. s, 1 H). 13C-NMR(CDCl
,
3
62.9 MHz): 135.8; 129.5; 128.3; 126.2; 113.0; 72.9; 42.4.
3-Phenoxy-2-hydroxypropyl Thiocyanate: IR(neat): 2163 s (SNC). 1H-NMR(CDCl 3, 250 MHz):
7.25 – 7.34 (m, 2 H); 6.89 – 7.04 (m, 3 H); 4.96 – 5.06 (m, 1 H); 4.20 (d, J ¼ 5.2, 2 H); 3.64 (d, J ¼ 7.1, 2 H ) .
13C-NMR(CDCl 3, 62.9 MHz): 158.0; 130.0; 122.0; 115.1; 114.9; 78.2; 67.2; 33.6.
2-Hydroxy-3-[(9-oxo-9H-thioxanthen-2-yl)oxy]propyl Thiocyanate: M.p. 108 – 1108. IR(KBr) 3381
(br.), 2157s (SCN), 1591s, 1560s, 1319s, 742s. 1H-NMR(CDCl 3, 250 MHz): 8.49 (d, J ¼ 8.0, 1 H); 7.91 (s,
1 H); 7.47 – 7.49 (m, 1 H); 7.33 – 7.39 (m, 3 H); 7.10 (d, J ¼ 8.8, 1 H); 4.30 – 4.37 (m, 1 H); 4.15 – 4.17 (m,
2 H); 3.13 – 3.34 (m, 2 H). 13C-NMR(CDCl 3, 62.9 MHz): 179.5; 156.7; 137.5; 132.2; 130.1; 130.0; 129.8;
128.3; 127.5; 126.3; 126.0; 122.6; 112.3; 111.3; 69.9; 68.8; 37.2. MS: 344 (0.1, [M þ 1]þ), 343 (4.6, Mþ), 300

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Helvetica Chimica Acta – Vol. 90 (2007)
(10.3), 268 (2.7), 227 (5.2), 171 (13.3) 200 (3.2). Anal. calc. for C17H13NO3S2 (343.42): C 59.46, H 3.82;
found: C 59.23, H 3.76.
3-[(1-Fluoro-9-oxo-9H-thioxanthen-4-yl)oxy]-2-hydroxypropyl Thiocyanate: M.p. 139 – 1408. IR
1
(KBr): 3076 (br.), 2161s (SCN), 1629s, 1591s, 1448s, 1251s. H-NMR((D )DMSO, 250 MHz): 8.33 (d,
6
J ¼ 8.1, 1 H); 6.67 – 7.85 (m, 2 H); 7.44 – 7.59 (m, 2 H); 7.25 – 7.33 (m, 1 H); 4.17 – 4.25 (m, 2 H). 13C-NMR
((D6)DMSO, 62.9 MHz): 135.1; 132.8; 129.4; 128.5; 126.9; 126.6; 115.6; 115.5; 113.3; 71.8; 67.5; 37.4. MS:
361 (0.5, Mþ), 246 (11.1), 245 (11.5), 218 (2.6), 217 (2.9), 189 (14.1), 157 (3.9), 125 (2.1), 73 (100). Anal.
calc. for C17H12FNO3S2 (361.41): C 56.50, H 3.35; found: C 56.87, H 3.39.
2-Hydroxy-3-(naphthalen-2-yloxy)propyl Thiocyanate: IR(neat): 3255 (br.), 2165 s (SCN), 2156s,
1
1673s, 1638s, 1387s, 1185s. H-NMR((D )DMSO, 250 MHz): 7.77 – 7.85 (m, 2 H); 7.41 – 7.45 (m, 3 H);
6
7.17 – 7.37 (m, 2 H); 4.31 – 4.41 (m, 2 H); 4.19 – 4.12 (m, 1 H); 3.27 – 3.55 (m, 2 H); 2.48 (s, 1 H). 13C-NMR
((D6)DMSO, 62.9 MHz): 155.7; 134.1; 129.4; 128.6; 127.5; 126.7; 126.5; 126.4; 123.8; 118.4; 107.1; 72.1;
67.3; 30.9. Anal. calc. for C14H13NO2S (259.32): C 64.84, H 5.05; found: C 64.52, H 4.93.
2-Hydroxy-3-(naphthalen-1-yloxy)propyl Thiocyanate: M.p. 230 – 2328. IR(KBr): 3250 (br.), 2160 s,
(SCN), 1678s, 1631s, 1390s, 1180s. 1H-NMR((D 6)DMSO, 250 MHz): 8.13 – 8.17 (m, 1 H); 7.84 – 7.88 (m,
1 H); 7.38 – 7.53 (m, 4 H); 6.98 – 7.01 (m, 1 H); 5.17 – 5.19 (m, 1 H); 4.37 – 4.52 (m, 2 H); 3.54 – 3.62 (m,
1 H); 3.35 – 3.44 (m, 1 H); 2.48 (s, 1 H). 13C-NMR((D )DMSO, 62.9 MHz): 162.4; 153.4; 133.9; 127.4;
6
126.5; 126.1; 125.4; 124.7; 121.4; 120.5; 105.5; 78.7; 68.0; 31.1. Anal. calc. for C14H13NO2S (259.32): C
64.84, H 5.05; found: C 64.65, H 4.91.
2-Hydroxy-3-(prop-2-enyloxy)propyl Thiocyanate: IR(neat): 2158 s (SCN). 1H-NMR(CDCl
,
3
250 MHz): 5.78 – 5.83 (m, 1 H); 5.10 – 5.25 (m, 2 H); 4.7 (br. s, 1 H); 3.61 – 3.98 (m, 3 H); 3.6 (d, J ¼ 7.0,
2 H); 3.36 (d, J ¼ 8.5, 2 H). 13C-NMR(CDCl 3, 62.9 MHz): 134.2; 118.0; 117.0; 80.2; 72.9; 69.2; 32.5.
3-Chloro-2-hydroxypropyl Thiocyanate: IR(neat): 2168 s (SCN). 1H-NMR(CDCl 3, 250 MHz):
4.03 – 4.08 (m, 1 H); 3.57 – 3.78 (m, 4 H); 2.64 (br. s, 1 H). 13C-NMR(CDCl 3, 62.9 MHz): 117.8; 71.2;
46.1; 43.4.
trans-2-Hydroxycyclohexyl Thiocyanate: IR(neat): 2165 s (SCN). 1H-NMR(CDCl 3, 250 MHz):
2.30 – 3.02 (m, 1 H); 2.11 – 2.30 (m, 1 H); 2.15 (s, 1 H); 1.41 – 1.81 (m, 2 H); 1.36 – 1.40 (m, 2 H); 1.20 –
1.50 (m, 4 H). 13C-NMR(CDCl 3, 62.9 MHz): 110.0; 72.0; 55.0; 34.5; 32.5; 30.5; 27.0.
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ReceivedFebruary 2, 2007