Synthesis and properties of novel macrocyclic compounds bearing thiourea moieties by use of chemical feature of hypervalent sulfur

Article abstract of DOI:10.1002/jhet.5570390128

Macrocyclic compounds 5a-i bearing two tetraazathiapentalene frameworks were synthesized by the reaction of 10-S-3 tetraazathiapentalene derivatives 3a-f with compounds having various diisothiocyanate functions 4a-e. The reduction of the macrocyclic compounds with NaBH₄ afforded the ring-opened macrocyclic compounds 11a-b and 11e-h by elimination of the hypervalent sulfur. The structures of these compounds were established by their spectral data and also by the X-ray crystallographic analysis of 11a. The other ring-opened macrocyclic compounds 14a and 14e-h that bear four thiourea groups were synthesized by alkaline hydrolysis of 5a and 5e-h in that elimination of the C=S^IV moiety in the tetraazathiapentalene rings occurred.

Full text of DOI:10.1002/jhet.5570390128

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds Bearing
Thiourea Moieties by Use of Chemical Feature of Hypervalent Sulfur
189
Noboru Matsumura,* Tsunao Konishi, Hirokazu Hayashi, Masanori Yasui,† Fujiko
Iwasaki,† and Kazuhiko Mizuno
Department of Applied Chemistry, Graduate School of Engineering,
Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
†Department of Applied Physics and Chemistry, The University of Electro-Communication, Tokyo 182-0021, Japan
Received July 13, 2001
Macrocyclic compounds 5a-i bearing two tetraazathiapentalene frameworks were synthesized by the reac-
tion of 10-S-3 tetraazathiapentalene derivatives 3a-f with compounds having various diisothiocyanate func-
tions 4a-e. The reduction of the macrocyclic compounds with NaBH afforded the ring-opened macrocyclic
4
compounds 11a-b and 11e-h by elimination of the hypervalent sulfur. The structures of these compounds
were established by their spectral data and also by the X-ray crystallographic analysis of 11a. The other
ring-opened macrocyclic compounds 14a and 14e-h that bear four thiourea groups were synthesized by alka-
IV
line hydrolysis of 5a and 5e-h in that elimination of the C=S moiety in the tetraazathiapentalene rings
occurred.
J. Heterocyclic Chem., 39, 189 (2002).
Introduction.
thiocarbonyl and carbonyl groups [7], respectively. We
have applied these reactions to the synthesis of macrocyclic
azacrown and azathiacrown ethers [8]. We have also found
that alkaline hydrolysis of 3a gives the ring-opened com-
pound 12 which bears two thiourea groups by elimination of
Since the discovery of an unusual structure of trithiapen-
talene [1], which is sometimes referred to as no bond reso-
nance, the chemistry of π-hypervalent heterocyclic systems
has been a subject of considerable interest. A number of π-
electron systems containing a 10-S-3 framework have been
synthesized [2], and their structures and reactivities have
also been investigated [2-3]. However, the characteristic
chemical properties of the apical and equatorial bonds on
the π-hypervalent atom have little been applied to organic
synthesis. Previously, we have reported the synthesis and
reactivities of 10-S-3 tetraazathiapentalene derivatives,
IV
the C=S moiety (see Scheme 7). On these backgrounds,
we planned to synthesize new macrocyclic compounds that
contain thiourea functions in the ring and also are soluble in
organic solvents. The anion binding abilities of thiourea
derivatives are much stronger than those of urea derivatives,
because of higher acidity of the former compounds [9-10].
Very recently, Umezawa et al. reported that receptors with a
rigid xanthene moiety show a strong complexation ability
toward dihydrogen phosphate anion through the thiourea
function in the xanthene moiety [11]. Therefore, macro-
cyclic compounds having thiourea function are expected to
serve as a receptor of inorganic anions in molecular recogni-
tion events [12]. In this paper, we report a new methodol-
ogy for preparing macrocyclic compounds bearing a
π-hypervalent sulfur in the ring and also the conversion of
these macrocyclic compounds to compounds bearing
thiourea functions by ring-opening reaction [13].
IV
namely 2,3-disubstituted 6,7-dihydro-5H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]indene-1,4(2H,3H)-
dithiones [4-5]. These compounds underwent unique reac-
tions that were attributable to the chemical nature of the
hypervalent sulfur. For example, the reaction of 3 (R = H)
with NaBH gave the ring-opened compound, 1,3-
4
bis(methylthiocarbamoyl)-perhydropyrimidine, in good
yield with release of the hypervalent sulfur [6], and the reac-
tion of 3 (R = H) with an excess of isothiocyanates and iso-
cyanates afforded tetraazathiapentalene derivatives having

190
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
Results and Discussion.
Synthesis of Macrocyclic Compounds.
5-Alkyl-3,4,5,6-tetrahydropyrimidine-2-thiols 1a-f, which
were prepared from 2-alkyl-1,3-diaminopropanes and carbon
disulfide under acidic conditions, were converted into dian-
ions 2a-f by treating with two equivalents of butyllithium in
THF at 0 °C under argon. The reaction of 2a-f with one
equivalent of phenacyl chloride, followed by addition of three
equivalents of methylisothiocyanate, gave tetraazathiapental-
ene derivatives 3a-f in moderate yields (Scheme 1). The
yields of 3a-f are shown in Table 1. The structures of 3a-f
1
were determined by their IR, H-NMR, mass spectra, and ele-
mental analyses. The compounds were colorless solids, sta-
ble in air, and highly soluble in organic solvents.

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
191
Treatment of 3a with 1 equivalent of p-xylylenediisothio-
cyanate (4a) in refluxing benzene for 24 hours gave the 18
membered macrocyclic compound 5a in 50% yield, along
with the monosubstituted tetraazathiapentalene derivative
6a in 17% yield and the disubstituted tetraazathiapentalene
derivative 7a in 3% yield (Scheme 2). This method is
referred to as Method A in this paper. The reaction of 3a-c
with diisothiocyanates 4a-b was carried out under similar
conditions. The results are summarized in Table 2.
We then studied the concentration dependence of 3a and
4a on the formation of 5a. The results are shown in Table
3. The change in the concentration of 3a did not affect the
yield of 5a (entries 1-3), but the yield of 5a slightly
decreased with increasing the reaction temperature (entry
4). On the other hand, when a 3:2 mixture of benzene and
hexane was used as solvent, the yield of 5a increased
markedly (entry 5).
Solubility.
In general, macrocyclic compounds bearing a π-hyper-
valent sulfur show a poor solubility in organic solvents. In
fact, 5 (R = H in 5a) is almost insoluble in any organic sol-
vent. However, introduction of longer alkyl chains on the
ring increases the solubility. Macrocyclic compounds 5a-c
are slightly soluble in ethanol, ether, acetone, and ethyl
acetate, but fairly soluble in CHCl , CH Cl and benzene.
3
2
2
The reaction of 3a-c with 4a gave the macrocyclic com-
pounds 5a-c in moderate yields (entries 1-3), but the reac-
tion of 3a with 4b afforded 5d in a low yield (entry 4). The
1
structures of 5a-d were determined by their IR, H NMR,
1
FAB mass spectra, and elemental analyses. The H NMR
spectrum of 5a in CDCl showed a singlet at δ 5.00 due to
3
benzylic protons and a singlet at δ 7.29 due to phenyl pro-
tons. The FAB mass spectrum of 5a showed a parent peak
+
(M +H) at 893.
Both of 6a and 7a changed to 5a upon refluxing in benzene
for 24 hours in 77% and 91% yields, respectively (Scheme 3).
These results suggest that 5a is derived via 6a and/or 7a.
The solubility of the macrocyclic compounds in CH Cl
decreased in the order of 5b > 5a > 5c > 5 (R = H in 5a)
(Table 4).
2
2
Exchange Reaction in Tetraazathiapentalene Rings of
Macrocyclic Compounds.
The reaction of 5a with excess of methylisothiocyanate
in refluxing benzene gave 6a, 7a, 3a, and 4a in 15, 4, 35,
and 32% yields, respectively, accompanying with the
recovery of 5a (Scheme 4).
This result indicates that the exchange reaction of the
NCS moiety in the tetraazathiapentalene ring of 5a is
occurring, and this is due to the weakness of the apical
bond of the hypervalent sulfur in the tetraazathiapentalene
ring. The tetraazathiapentalene derivative 8 in solid state
is stable in air, but decomposes slowly in solution. In fact,
1
the H NMR spectrum revealed that 8 decompose in ben-

192
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
zene to give the thiadiazole derivative 9 and the isoseleno-
cyanate 10 (Scheme 5).
When Method B was employed, the yields of the macro-
cyclic compounds were remarkably improved (entries 1-
4). However, for 3f and 4c that have bulky group, the
yields of the macrocyclic compounds 5i and 5e were not
improved even by employing Method B. The structures of
the macrocyclic compounds 5d-i were determind by their
Furthermore, 9 undergoes a 1,3-dipolar cycloaddition
with 10 to give 8 in good yield. These results suggest that in
the reaction shown in Scheme 2, the removal of methylisoth-
iocyanate produced during the reactions serves as a proce-
dure for improving the yields of the macrocyclic com-
pounds. Based on this result, compound 5d was quantita-
tively obtained by the following procedure (Method B): A
mixture of 3a and 2 equivalents of trimethyleneisothio-
cyanate 4b was refluxed in benzene for 24 hours, followed
by removal of benzene under reduced pressure. After
addition of benzene and n-hexane to the residue, the mixture
was refluxed for 2 hours. The solvent mixture was again
removed under reduced pressure. These operations were
repeated three times to give 5d. This method (Method B)
was applied to the reaction of tetraazathiapentalene deriva-
tives 3a, 3d, and 3f with a variety of diisothiocyanates. As
diisothiocyanates, we used p-xylylenediisothiocyanate (4a),
9,10-bis(isothiocyanatomethyl)anthracene (4c), N,N-bis(2-
isothiocyanatomethyl)amine (4d), and m-xylylenediisothio-
cyanate (4e). The reactions of 3a, 3d, and 3f with 4a-e was
carried out by both of Method A and Method B. The results
are summarized in Table 5.
1
IR, H NMR spectra, and elemental analyses.
Reduction of Macrocyclic Compounds.
Previously, we have reported that 3 (R = H) is con-
verted into the ring-opened compound, 1,3-bis(methyl-
thiocarbamoyl)perhydropyrimidine, by elimination of
the hypervalent sulfur upon treating with NaBH [6].
4
We applied this reaction to the ring-opening reaction of
the macrocyclic compounds 5a-5b, and 5e-h. For
example, the reaction of 5a with NaBH in DMSO at
4
room temperature for 24 hours afforded the 26–mem-
bered macrocyclic compound 11a that contains four
thiourea moieties in the ring in 66% yield. The other
macrocyclic compounds 5b and 5e-h reacted similarly
with NaBH to give the macrocyclic compounds 11b
4
and 11e-h in moderate yields (Scheme 6). The results
are summarized in Table 6.
The structures of 11a-b and 11e-h were determined by
1
their IR, H NMR and MS spectra, and elemental analyses.

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
193
thiourea 12 and 5-octyl-2-oxo-dihydro-pyrimidine-1,3-
dicarbothioic acid bismethylamide 13 in 28% and 37%
yields, respectively [13].
We also found that treatment of 13 with an aqueous EtOH-
KOH solution under the similar conditions gave 12 in 69%
yield (Scheme 7). These results clearly show that the conver-
sion of 3a into 12 proceeds via cyclic urea intermediate such
as 13. We applied this alkaline hydrolysis reaction to 5a and
5e-h. For example, treatment of 5a with an aqueous EtOH-
KOH solution gave the 30-membered macrocyclic com-
pound 14a that has four thiourea moieties in the ring in 44%
Figure 1. ORTEP drawing of 11a [15]. 10 H atoms and solvent mole-
cules are omitted. The molecule has a crystallographic center of sym-
metry at the center of the macrocycle. Symmetry code: i (1-x, -y, 2-z).
Selected bond lengths (A) and angles (degrees): S1-C1=1.70(2),
N1-C1=1.36(2), N1-C14=1.43(2), N2-C1=1.38(2), N2-C2=1.43(2),
N2-C3=1.49(2), C1-N1-C14=124(2), C1-N2-C2=125(2), N1-C1-
N2=117.4(14), C2-N2-C3= 110(2).
lV
yield with elimination of the C=S function of the tetraaza-
The structure of 11a was further confirmed by an X-ray
crystallographic analysis [14]. Figure 1 shows an ORTEP
drawing of 11a [15]. The distance between two benzene
rings was about 4.0 Å.
thiapentalene ring. The other macrocyclic compounds 5e-h
reacted similarly with an aqueous EtOH-KOH solution to
give 14e-h in moderate yields (Scheme 8). The structures of
14a and 14e-h were determined by comparison of their spec-
Alkaline Hydrolysis of Macrocyclic Compounds.
trtal data with
those of 11a-b and 11e-h, and elemental analy-
We have found that treatment of 3a with an aqueous
EtOH- KOH solution gave the ring-opened product,
1-methyl-3-{2-[(3-methyl-thioureido)-methyl]-decyl}-
ses. The results are summarized in Table 7. The conversion
of 5a and 5e-h into 14a and 14e-h is considered to proceed
via carbonyl intermediate such as 13 shown in Scheme 7.

194
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
IV
moieties by release of the C=S function. These macro-
cyclic compounds are supposed to have potential as an
anion receptor in the host-guest chemistry. The method-
ology reported in this paper would provide a useful tool
for the synthesis of macrocyclic compounds containing
thiourea function.
EXPERIMENTAL
All the solvents used in this study were purified by usual pro-
cedures. TLC was performed on a Merck Art 25 DC-plastikfolien
Kieselgel 60 F . Column chromatography was performed on
254
silica gel (Merck, 70-230 mesh). NMR spectra were obtained
with a Varian Murcury 300 NMR spectrometer. Chemical shifts
are expressed in ppm with TMS as an internal standard. Melting
points were determined with a Yanaco MP-500 and are uncor-
rected. Infrared spectra were recorded by a Jasco Herschel FT IR
230 or a PERKIN ERMER 1600. UV spectra were taken with a
SHIMADU UV-160A. MS spectra were obtained on a JEOL-DX
303HF. Elemental analysis were done on a YANAGIMOTO
CHN corder MT-3.
Conclusions.
In summary, we synthesized successfully new tetraaza-
thiapentalene derivatives having long alkyl-chains and a
hypervalent sulfur. These hypervalent compounds were
converted into macrocyclic compounds bearing two
azathiapentalene rings by utilizing the chemical
tetra
nature of apical and equatorial bonds of the hypervalent
Materials.
p-Xylylenediisothiocianate (4a), m-xylylenediisothiocianate
(4e), 2-octyldiethylmalonate, 2-dodecyldiethyl malonate, 2-octa-
decyldiethyl malonate, 2-octylmalone diamide, 2-dodecyl-
malonediamide, and 2-octadecylmalone diamide were prepared
according to the procedures described in literatures [16-17].
sulfur. The reduction with NaBH of the macrocyclic
4
compounds having tetraazathiapentalene rings gave ring-
opened rigid macrocyclic compounds bearing thiourea
function by the reductive desulfurization of the hyperva-
lent sulfur. Their structures were confirmed by their spec-
tral data and X-ray crystallographic analysis. On the
other hand, alkaline hydrolysis of the macrocyclic com-
pounds having the hypervalent sulfur afforded flexible
macrocyclic compounds containing four thiourea
Preparation of 5-Alkyl-3,4,5,6-tetrahydroprimidine-2-thiols 1a-f.
5-Alkyl-3,4,5,6-tetrahydropyrimidine-2-thiols 1a-f were pre-
pared in a similar manner to that reported in literature [18-19].
They were prepared according to the following procedure: 1)
Alkylation of dimethyl malonate, 2) conversion of dimethyl-
malonates to amides, 3) reduction of amides to amines, and 4)
cyclization of diamines by use of CS .
2

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
195
2-(4-Benzyloxybutyl)dimethyl malonate.
reduced pressure. The crude product of 2-(4-benzyloxybutyl)-1,3-
diaminopropane was used for the next step without purification.
A solution of 4-bromobutyl benzyl ether (243 mg, 1 mmol) in
DMF (8 mL) was added to a mixture of dimethyl malonate (132
5-(4-Benzyloxybutyl)-3,4,5,6-tetrahydropyrimidine-2-thiol (1d).
mg,1 mmol) and K CO 276 mg, 2 mmol) in DMF (7 mL) at
2
3
Half of an ethanol solution containing CS (1.142 g, 15 mmol)
was added to a solution of crude 2-(4-benzyloxybutyl)-1,3-
2
room temperature under argon. The mixture was stirred at the
same temperature for 24 hours, and then extracted with CH Cl .
2
2
diaminopropane in EtOH-H O under ice-cooling. The mixture
2
The CH Cl extract was washed with water, dried (Na SO ), and
2
2
2
4
was warmed to 60 °C, and then the other half of the CS ethanol
2
evaporated under reduced pressure. The residue was purified by
column chromatography on silica gel with toluene-AcOEt (9:1
v/v). 2-(4-Benzyloxybutyl)dimethylmalonate was obtained in
82% yield (242 mg) as an oil, bp 110°/ 5 mmHg; ir (potassium
bromide): 3036, 2960, 2859, 1735, 1448, 1360, 1249, 1153, 1031,
solution was added at the same temperature. The reaction mixture
was refluxed for 5 hours, concentrated HCl solution (1 mL) was
added, and then further refluxed for 18 hours. The solvent was
removed and the residue was extracted with CH Cl . The extract
2
2
was washed with brine, dried (Na SO ) and evaporated under
2
4
-1
1
817, and 743 cm ; H nmr (300 MHz, deuteriochloroform): δ
137-1.44 (m, 2H), 1.61-1.67 (m, 2H), 1.92 (q, 2H), 3.36 (t, 1H),
3.46 (t, 2H), 3.72 (s,6H), 4.48 (s, 2H), 7.27-7.35 (m,5H).
reduced pressure. The product was purified by column chromatog-
raphy on silica gel with CH Cl –AcOEt (9:1 v/v). Compound 1d
2
2
was obtaind in 58% yield (1.264 g) as colorless solid, mp 128-
130°; ir (potassium bromide): 3229, 2930, 2857, 1553, 1497, 1454,
Anal. Calcd. for C
H O : C, 65.29; H, 7.53. Found: C,
16 22 5
65.20; H, 7.57.
-1
1
1366, 1203, 1116, and 751 cm ; H nmr (300 MHz, deuteriochlo-
roform): δ 1.17-1.40 (m, 4H), 1.52 (q, 2H), 1.86 (m, 1H), 2.87 (br
t, 2H), 3.26 (br d, 2H), 3.39 (t, 2H, J = 6.7Hz), 4.41 (s, 2H), 6.94
(br, 2H), 7.26-7.29 (m, 5H).
2-(4-Benzyloxybutyl)malone diamide.
A catalytic amount (500 mg) of Na was added to an NH satu-
3
rated cooled methanol, and 2-(4-benzyloxybutyl)dimethyl-
malonate (331 mg, 1.1 mmol) was added to this mixture. The
mixture was stirred at room temperature for 3 days. The precipi-
tates were isolated by filtration, washed with methanol, and dried
in vacuo. 2-(4-Benzyloxybutyl)malone diamide was obtained in
98% yield (302 mg) as colorless solid, mp 183-184° (decomp); ir
(potassium bromide): 3377, 3297, 3198, 2944, 2855, 1671, 1498,
Anal. Calcd. for C
Found: C, 64.47; H, 8.22; N, 9.76.
H N OS: C, 64.71; H, 7.96; N, 10.06.
15 22 2
2-(4-Phenoxybutyl)dimethyl malonate.
2-(4-Phenoxybutyl)dimethylmalonate was obtained in 70%
yield (2.273 g) from 4-bromophenyl butyl ether and dimethyl-
malonate,: bp 240°/ 12mmHg; ir (potassium bromide): 2953,
2869, 1734, 1559, 1542, 1497, 1436, 1244, 1033, 884, and 693
-1 1
1475, 1458, 1451, 1382, 1278, 1250, 1114, and 696 cm ; H nmr
(300 MHz, dimethylsulfoxide-d ): δ 1.23-1.31 (m, 2H), 1.47-
-1 1
6
cm ; H nmr (300 MHz, deuteriochloroform): δ 1.47 (m, 2H),
1.67 (m, 2H), 1.96 (m, 2H), 3.73 (t, 1H), 3.75 (s, 6H), 3.95 (t,
2H), 6.88 (m, 3H), 7.22 (m, 5H).
1.58 (m, 2H), 1.66 (q, 2H, J = 6.7 Hz), 3.39 (t, 2H, J = 6.7 Hz),
4.43 (s, 2H), 7.03 (br,2H), 7.29-7.37 (m, 7H).
Anal. Calcd. for C
H N O : C, 63.62; H, 7.63; N, 10.60.
Anal. Calcd. for C
66.37; H, 3.83.
H O : C, 66.67; H, 3.73. Found: C,
14 20 2 3
15 10 5
Found: C, 63.90; H, 7.72; N, 10.30.
2-(4-Benzyloxybutyl)-1,3-diaminopropane.
A mixture of 2-(4-benzyloxybutyl)malone diamide (2.0 g, 9.3
2-(9-Anthrylmethyl)dimethyl malonate.
2-(9-Anthrylmethyl)dimethyl malonate was obtained in 40%
yield (4.807g) from 9-bromomethylanthracene and dimethy-
malonate, mp 128-130°; ir (potassium bromide): 2152, 2909,
1734, 1654, 1560, 1437, 1284, 754, and 690 cm ; H nmr (300
MHz, deuteriochloroform): δ 3.59 (s, 6H), 3.88 (t, 1H, J =
7.4Hz), 3.95 (d, 2H, J = 7.4Hz), 7.58 (m, 5H), 8.31 (m, 2H), 8.65
(m, 2H).
mmol) and BH -THF complex (46.7 mL, 46.7 mmol) in THF (50
3
mL) was refluxed under argon for 3 hours, cooled to room tempera-
ture, and then 6 M HCl (7 mL) was added to the mixture. The THF
solution was evaporated, and the residue was extracted under an
alkaline condition (pH = 11) with diethyl ether. The ether extract
-1
1
was washed with water, dried (Na SO ), and evaporated under
2
4

196
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
2-(4-Phenoxybutyl)malone diamide.
-
3278, 2928, 2855, 1560, 1271, 1202, 1114, 985, 750, and 698 cm
1
1
; H nmr (300 MHz, deuteriochloroform): δ 1.44 (m, 2H), 1.53
(m, 2H), 1.79 (m, 2H), 1.98 (m, 1H), 2.99 (br t, 2H), 3.40 (br d,
2H), 3.95 (t, 2H), 6.96 (m, 3H), 7.08 (br, 2H), 7.30 (m, 2H).
2-(4-Phenoxybutyl)malone diamide was obtained in 92% yield
(3.299g) from2-(4-phenoxybutyl)dimethylmalonate and NH ,
mp 230° (decomp); ir (potassium bromide): 3368, 3191, 2938,
3
-1
Anal. Calcd. for C
H N OS: C, 63.60; H, 7.62; N, 10.59.
2858, 1670, 1468, 1382, 1246, 1177, 1035, 893, and 696 cm ;
14 20 2
1
Found: C, 63.72; H, 7.59; N, 10.60.
H nmr (300 MHz, dimethylsulfoxide-d ): δ 1.38 (m, 2H), 1.70
6
(m, 4H), 2.98 (t, 1H, J = 6.4Hz), 3.92 (t, 2H, J = 7.4Hz), 6.90 (m,
5H), 7.03 (br, 2H), 7.26 (m, 2H).
5-(9-Anthrylmethyl)-3,4,5,6-tetrahydropyrimidine-2-thiol (1f).
5-(9-Anthrylmethyl)-3,4,5,6-tetrahydropyrimidine-2-thiol (1f)
was obtained in 8% yield (192 mg) from 2-(9-anthrylmethyl)-
Anal. Calcd. for C
H N O : C, 62.38; H, 7.25; N, 11.24.
13 18 2 3
Found: C, 62.31; H, 7.25; N, 11.22.
1,3-diaminopropane and CS , mp 275-277° (decomp); ir (potas-
2
2-(9-Anthrylmethyl)malone diamide.
sium bromide): 3188, 3091, 2875, 2857, 1576, 1559, 1490, 1458,
-1
1439, 1377, 1324, 1301, 1217, 1028, 900, 751, and 684 cm ; uv
2-(9-Anthrylmethyl)malone diamide was obtained in 87%
yield (3.801 g) from 2-(9-anthrylmethyl)dimethylmalonate and
(CH Cl ) λmax 402 (logε 3.88), 380 (logε 3.90), 361 (logε 3.68),
2
2
1
257 (logε 4.72) nm; H nmr (300 MHz, deuteriochloroform): δ
2.60 (m, 1H), 3.23 (br t, 2H), 3.32 (br d, 2H), 3.75 (d, 2H, J = 7.7
Hz), 6.27 (br, 2H), 7.62 (m, 5H), 8.21 (d, 2H, J = 7.1 Hz).
NH , mp 247° (decomp); ir (potassium bromide): 3385, 3186,
3
-1
1
2909, 2849, 1718, 1684, 1637, 901, 750, and 686 cm ; H nmr
(300 MHz, dimethylsulfoxide-d ): δ 4.08 (d, 2H, J = 6.3Hz),
6
Anal. Calcd. for C
H N S: C, 74.35; H, 5.91; N, 9.29.
7.14 (br, 2H), 7.24 (br, 2H), 7.67 (m, 5H), 8.45 (d, 2H, J =
19 18 2
+
Found: C, 74.60; H, 5.65; N, 9.19.
10.7Hz), 8.50 (d, 2H, J = 11.2Hz); FAB mass m/e 292 ( M+H ).
IV
2,3-Dimethyl-6-octyl-5H,7H-2a-thia(2a-S )-2,3,4a,7a-tetraaza-
cyclopent[c,d]indene-1,4(2H,3H)–dithione (3a).
5-Octyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1a).
5-Octyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1a) was
Typical procedure is as follows: A hexane solution of butyl-
lithium (1.9 mmol) was added to a solution of cyclic thiourea 1a
(200 mg, 0.88 mmol) in THF (15 ml) with stirring at 0 °C under
argon. The mixture was stirred for 1 hour at the same temperature.
To the resulting dianion 2a was added dropwise a THF solution (5
ml) of phenacyl chloride (135 mg, 0.88 mmol). The solution imme-
diately became wine red. The reaction mixture was refluxed for 2
hours under argon and cooled to room temperature. A solution of
methylisothiocyanate (192 mg, 2.7 mmol) in THF (5 mL) was
added, and the mixture was stirred at room temperature for 20 hours
under argon, and then evaporated. The residue was poured into an
obtained in 70% yield (1.489 g) from 2-octyl-1,3-diamino-
propane and CS (1.421 g, 18 mmol) under an acidic condition,
2
mp 139-140°; ir (potassium bromide): 3210, 3100, 2973, 2950,
2922, 2852, 1574, 1557, 1466, 1392, 1352, 1295, 1276, 1215,
-1
722, 637, and 619 cm ; uv (CH CN) λmax 252 (logε 4.22) nm;
3
1
H nmr (300 MHz, deuteriochloroform): δ 0.88 (t, 3H, J = 6.7
Hz), 1.27-1.31 (m, 14H), 1.96 (m, 1H), 2.95 (dd, 2H, J = 12.2 Hz
and 10.4 Hz), 3.31-3.39 (m, 2H), 6.60 (br, 2H).
Anal. Calcd. for C
H N S: C, 63.10; H, 10.59; N, 12.27.
12 24 2
Found: C, 63.02; H, 10.47; N, 12.00.
5-Dodecyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1b).
aqueous NH Cl solution. The solution was extracted with CH Cl
4
2
2,
5-Dodecyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1b) was
obtained in 72% yield (3.062g), mp 137-138°; ir (potassium
bromide): 3205, 3100, 2976, 2962, 2951, 2921, 2850, 1574,
and the extract was washed with water, dried (Na SO ), and con-
2 4
centrated under reduced pressure. The residue was chro-
matographed on a silica gel with CH Cl -n-hexane (20:1 v/v) to
2
2
-1
1557, 1466, 1391, 1289, 1271, 1218, 721, 638, and 620 cm ; uv
give 3a (215mg, 66%) as a colorless solid, mp 156-158°; ir (potas-
1
(CH CN) λmax 252 (logε 4.26) nm; H nmr (300 MHz, deuterio-
sium bromide): 2924, 2852, 1585, 1541, 1492, 1468, 1238, 1200,
3
-1
chloroform ): δ 0.88 (t, 3H, J = 6.7Hz), 1.26-1.31 (m, 22H), 1.95
(m, 1H), 2.95 (dd, 2H, J = 12.2Hz and 10.4Hz), 3.31-3.39 (m,
2H), 6.61 (br, 2H).
1172, 1118, 1099, 724, and 646 cm ; uv (CH CN) λmax 260 (logε
3
1
4.52) nm; H nmr (300 MHz, deuteriochloroform): δ 0.89 (t, 3H, J =
6.7 Hz), 1.28-1.55 (m, 14H), 2.23 (m, 1H), 3.23 (s, 6H), 3.59 (dd,
2H, J = 13.9 Hz and 9.9 Hz), 4.87 (dd, 2H, J = 13.9 Hz and 4.5 Hz ).
Anal. Calcd. for C
H N S: C, 67.55; H, 11.34; N, 9.85.
16 32 2
Anal. Calcd. for C
H N S : C, 51.57; H, 7.57; N, 15.04.
Found: C, 67.59; H, 11.61; N, 9.73.
16 28 4 3
Found: C, 51.51; H, 7.73; N, 14.58.
5-Octadecyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1c).
IV
2,3-Dimethyl-6-dodecyl-5H,7H-2a-thia(2a-S )-2,3,4a,7a-
tetraazacyclopent[c,d]indene-1,4(2H,3H)–dithione (3b).
5-Octadecyl-3,4,5,6-tetrahydropyrimidine-2-thiol (1c) was
obtained in 13% yield (1.623 g) from 2-octadecyl-1,3-diamino-
propane and CS , mp 132-133°; ir (potassium bromide): 3202,
Tetraazathiapentalene 3b was obtained in 66% yield (283 mg)
2
3102, 2951, 2919, 2850, 1576, 1557, 1472, 1352, 1286, 1273,
by use of the 2b/PhCOCH Cl/MeNCS system, mp 148-152°; ir
(potassium bromide): 2923, 2852, 1586, 1542, 1492, 1469, 1240,
2
-1
1218, 721, and 637 cm ; uv (CH Cl ) λmax 254 (logε 4.19) nm;
2
2
1
-1
H nmr (300 MHz, deuteriochloroform): δ 0.88 (t, 3H, J =
1201, 1173, 1123, 1107, and 646 cm ; uv (CH Cl ) λmax
2
2
1
6.7Hz), 1.25-1.31 (m, 34H), 1.96 (m, 1H), 2.96 (dd, 2H, J =
12.2Hz and 10.4Hz), 3.32-3.39 (m, 2H), 6.34 (br, 2H).
263(logε 4.56) nm; H nmr (300 MHz, deuteriochloroform): δ
0.88 (t, 3H, J = 6.7 Hz), 1.28-1.53 (m, 22H), 2.23 (m, 1H), 3.23
(s, 6H), 3.59 (dd, 2H, J = 13.9 Hz and 9.9 Hz), 4.88 (dd, 2H, J =
13.9 Hz and 4.5 Hz).
Anal. Calcd. for C
H N S: C, 71.67; H, 12.03; N, 7.60.
22 44 2
Found: C, 71.92; H, 11.84; N, 7.47.
Anal. Calcd. for C
H N S : C, 56.03; H, 8.46; N, 13.07.
5-(4-Phenoxybutyl)-3,4,5,6-tetrahydropyrimidine-2-thiol (1e).
20 36 4 3
Found: C, 56.13; H, 8.67; N, 12.95.
5-(4-Phenoxybutyl)-3,4,5,6-tetrahydropyrimidine-2-thiol (1e)
IV
was obtained in 27% yield (962 mg) from 2-(4-phenoxybutyl)-1,3-
2,3-Dimethyl-6-octadecyl-5H,7H-2a-thia(2a-S )-2,3,4a,7a-
tetraazacyclopent[c,d]indene-1,4(2H,3H)–dithione (3c).
diaminopropane and CS , mp 168-169°; ir (potassium bromide):
2

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
197
Tetraazathiapentalene 3c was obtained in 46% yield (238 mg)
by use of the
The same reaction was conducted by employing benzene-n-
hexane as solvent system: A solution of 3a (373 mg, 1 mmol) and 4a
(220 mg, 1 mmol) in a 3:2 mixture (10 mL) benzene and n-hexane
was refluxed for 24 hours, and cooled to room temperature. The pre-
cipitate was isolated by filtration, washed with n-hexane, and dried
under reduced pressure. Compound 5a was obtained in a 77% yield
(745 mg) as colorless solid. On the other hand, the filtrate was
removed under reduced pressure and the residue was purified by col-
umn chromatography on silica gel with CH Cl :n-hexane = 3: 1
2c/PhCOCH Cl/MeNCS system, mp 148-152°; ir (potassium
2
bromide): 2921, 2851, 1586, 1541, 1490, 1238, 1201, 1172, 1111,
-1
1
1094, and 646 cm ; uv (CH Cl ) λmax 264 (logε 4.58) nm; H
2
2
nmr (300 MHz, deuteriochloroform): δ 0.88 (t, 3H, J = 6.7Hz),
1.26-1.53 (m, 34H), 2.22 (m, 1H), 3.23 (s, 6H), 3.58 (dd, 2H),
4.88 (dd, 2H).
Anal. Calcd. for C
H N S : C, 60.89; H, 9.43; N, 10.92.
2
2
26 48 4 3
(v/v) to give 6a (29 mg, 6%) and 7a (7 mg, 1%).
Found: C, 61.09; H, 9.12; N, 10.68.
IV
2) Method B.
2,3-Dimethyl-6-(4-benzyloxybutane)-5H,7H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]indene-1,4(2H,3H)–dithione (3d).
A mixture of 3a (373 mg, 1 mmol) and 4a (220 mg, 1 mmol) in
benzene was refluxed for 24 hours, and benzene was removed in
vacuo. A 3:2 (v/v) mixture (10 mL) of benzene and n-hexane was
added to the residue, and refluxed for 2 hours. The solvent was
removed under reduced pressure. These operations were repeated
three times. Products were purified by the same method as those used
for Method A. Compound 5a was obtained in a quantitative yield.
Tetraazathiapentalene 3d was obtained in 46% yield (196 mg) by
use of the 2d/PhCOCH Cl/MeNCS system, mp 101-103°; ir (potas-
2
sium bromide): 2921, 2849, 1578, 1541, 1490, 1458, 1388, 1239,
-1
1200, 1113, 750, 693, and 675 cm ; uv (CH Cl ) λmax 263 (logε
2
2
1
4.90) nm; H nmr (300 MHz, deuteriochloroform): δ 1.55 (m, 6H),
2.22 (m, 1H), 3.23 (s, 6H), 3.49 (t, 2H, J = 5.8 Hz), 3.58 (t, 2H, J =
13.1 Hz), 4.51(s, 2H), 4.87(d, 2H, J = 13.1 Hz), 7.36(m, 5H).
Macrocyclic Compound (5a).
Anal. Calcd. for C
H N OS : C, 54.04; H, 6.21; N, 13.27.
19 26 4 3
Compound 5a has mp 223-225° (decomp); ir (potassium bro-
mide): 2922, 2853, 1575, 1528, 1477, 1417, 1235, 1198, 1163,
Found: C, 54.21; H, 6.19; N, 13.53.
-1
IV
1144, 1132, and 1106 cm ; uv (CH Cl ) λmax 266 (logε 4.74)
2,3-Dimethyl-6-(4-phenoxybutane)-5H,7H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]indene-1,4(2H,3H)–dithione (3e).
2
2
1
nm; H nmr (300 MHz, deuteriochloroform): δ 0.89 (t, 6H, J =
6.7 Hz), 1.27-1.55 (m, 28H), 2.16 (m, 2H), 3.47 (dd, 4H, J = 13.4
Hz and 10.4 Hz), 4.89 (dd, 4H, J = 13.4 Hz and 10.4 Hz), 5.00 (s,
Tetraazathiapentalene 3e was obtained in 80% yield (322 mg)
by use of the 2e/PhCOCH Cl/MeNCS system, mp 165-167°; ir
2
+
8H), 7.29 (s, 8H); FAB-mass m/z 893(M+H ).
(potassium bromide): 2940, 2857, 1581, 1540, 1498, 1466, 1389,
1276, 1243, 1198, 1173, 1121, 1032, 933, 814, 754, and 689
Anal. Calcd. for C
H N S : C, 59.15; H, 6.77; N, 12.54.
44 60 8 6
Found: C, 58.98; H, 6.82; N, 12.65.
-1
1
cm ; H nmr (300 MHz, deuteriochloroform): δ 1.67 (m, 4H),
1.85 (m, 2H), 2.27 (m, 1H), 3.23 (s, 6H), 3.49 (dd, 2H, J = 9.9 Hz
and 3.8 Hz), 4.00 (t, 2H, J = 6.0 Hz), 4.89 (dd, 2H, J = 4.4 Hz and
9.3 Hz), 6.94 (m, 3H), 7.29 (m, 2H).
2-(4-Isothiocyanatomethyl-benzyl)-3-methyl-6-octyl-5H,7H-2a-
IV
thia(2a-S )-2,3,4a,7a-tetraazacyclopenta[cd]-indene-
1,4(2H,3H)-dithione (6a).
Anal. Calcd for C
Found: C, 53.23; H, 6.03; N, 13.42.
H N OS : C, 52.95; H, 5.92; N, 13.72.
18 24 4 3
Compound 6a has mp 215-217° (decomp); ir (potassium
bromide): 2926, 2854, 2189, 2097, 1579, 1531, 1484, 1466,
1427, 1406, 1342, 1236, 1189, 1173, 1130, 1101, and 720
IV
2,3-Dimethyl-6-(9-anthrylmethyl)-5H,7H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]indene-1,4(2H,3H)–dithione (3f).
-x1
1
cm ; uv (CH Cl ) λmax 264 (logε 4.50) nm; H nmr (300
2
2
MHz, deuteriochloroform): δ 0.89 (t, 3H, J = 6.7 Hz), 1.28-
1.54 (m, 14H), 2.23 (m, 1H), 3.18 (s, 6H), 3.51-3.62 (m, 2H),
4.69 (s, 2H), 4.85-4.96 (m, 4H), 7.27-7.41 (m, 4H).
Tetraazathiapentalene 3f was obtained in 45% yield (81 mg) by
use of the 2f / PhCOCH Cl/MeNCS system; Yellow solid, mp
2
145-146°; ir (potassium bromide): 3039, 2922, 2849, 1676, 1578,
1541, 1490, 1444, 1401, 1280, 1199, 1055, 1011, 887, 756, and
Anal. Calcd for C
H N S : C, 55.45; H, 6.40; N, 13.47.
24 33 5 4
Found: C, 55.29; H, 6.25; N, 13.32.
-1
679 cm ; uv (CH Cl ) λmax 389 (logε 4.06), 378 (logε 3.88),
2
2
1
360 (logε 3.96), 256 (logε 5.11) nm; H nmr (300 MHz, deuterio-
chloroform): δ 2.80 (m, 1H), 3.18 (s, 6H), 3.86 (d, 2H, J = 6.0
Hz), 3.91 (d, 2H, J = 11.4 Hz), 4.64 (t, 2H, J = 12.9 Hz), 7.62 (m,
5H), 8.01 (t, 2H, J = 8.8 Hz).
2,3-Bis-(4-isothiocyanatomethyl-benzyl)-6-octyl-5H,7H-2a-
IV
thia(2a-S )-2,3,4a,7a-tetraazacyclopenta[cd]-indene-
1,4(2H,3H)-dithione (7a).
Compound 7a has mp 209-211° (decomp); ir (potassium bro-
mide: 2925, 2854, 2090, 1579, 1532, 1474, 1420, 1406, 1334,
Anal. Calcd for C
H N S : C, 61.30; H, 4.92; N, 12.43.
23 22 4 3
Found: C, 61.00; H, 5.22; N, 12.17.
Synthesis of Macrocyclic Compound (5a).
1) Method A.
-1
1236, 1198, 1163, 752, 724, and 671 cm ; uv (CH Cl ) λmax
2
2
1
265 (logε 4.54) nm; H nmr (300 MHz, deuteriochloroform): δ
0.89 (t, 3H, J = 6.7Hz), 1.28-1.53 (m, 14H), 2.22 (m, 1H), 3.52
(m, 2H), 4.71 (s, 2H), 4.87-4.95 (m, 4H), 7.25-7.35 (m, 4H).
A solution of 3a (373 mg, 1 mmol) and 4a (220 mg, 1 mmol)
in benzene (10 mL) was refluxed for 24 hours, and cooled to
room temperature. The precipitate was isolated by filtration,
washed with n-hexane, and dried in vacuo. Compound 5a was
obtained in 50% yield (224 mg) as colorless solid. On the other
hand, the filtrate was evaporated, and the residue was purified by
Anal. Calcd for C H N S : C, 57.62; H, 5.74; N, 12.60.
Found: C, 57.86; H, 5.76; N, 12.38.
32 38 6 5
Conversion of 6a to 5a.
Compound 6a (166 mg, 0.32 mmol) was refluxed in benzene
(25 mL) for 24 hours. The precipitate was isolated by filtration,
washed with n-hexane, and dried in vacuo. Compound 5a was
obtained in 77% yield (110 mg). After the filtrate was removed
column chromatography on silica gel with CH Cl -n-hexane (3:1
2
2
v/v) to give 6a (82 mg, 17%) and 7a (21 mg, 3%).

198
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
in vacuo, the crude product was purified by column chromatogra-
phy (silica gel, CH Cl :n-hexane = 9 : 1 v/v) to give 4a (5 mg,
Anal. Calcd. for C H N OSSe: C, 44.17; H, 4.02; N, 12.88
12 13 3
Found: C, 44.00; H, 4.01; N, 13.00.
2
2
7%), 7a (trace), and 3a (20 mg, 17%).
IV
2,3-Bis(p-methoxyphenyl)-6,7-dihydro-5H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]inden-1,4(2H,3H)-diselenone (8).
Conversion of 7a to 5a.
Compound 7a (77 mg, 0.12 mmol) was refluxed in benzene (9
mL) for 24 hours. The precipitate was isolated by filtration,
washed with n-hexane and dried in vacuo. Compound 5a was
obtained in 91% yield (47 mg). After the filtrate was evaporated
under reduced pressure, the residue was purified by column chro-
matography (silica gel, CH Cl :n-hexane = 9:1 v/v) to give 4a
Compound 8 has mp 146-148°(decomp); ir (potassium bro-
mide): 2930, 2833, 2130, 1606, 1563, 1514, 1447, 1311, 1251,
1210, 1148, 1084, 1033, 979, 884, 834, 779, 731, 684, 563, 521,
-1
and 500 cm ; uv (CH Cl ) λmax 288 (logε 4.38), 352 (logε
2
2
1
3.84) nm; H nmr (300 MHz, deuteriochloroform): δ 2.51 (m,
2H), 4.69 (t, 4H, J = 5.8 Hz), 6.90-7.30 (m, 8H).
2
2
(23 mg, 91%).
Anal. Calcd. for C
H N OSSe: C, 44.17; H, 4.02; N, 12.88
12 13 3
Found: C, 44.00; H, 4.01; N, 13.00.
The Reaction of 5a with Methylisothiocyanate.
Thermolysis of 8.
A solution of 5a (134 mg, 0.15 mmol) and methylisothicyanate
(78 mg, 1.05 mmol) in benzene (15 mL) was refluxed for 24
hours. After the solvent was removed in vacuo,
Compound 8 in solid state was stable to air, but decomposed
slowly in benzene or CHCl solution (see Scheme 5). When the
3
1
CH Cl -n-hexane was added to the residue. The precipitate
H NMR spectrum of 8 was measured immediately after dissolv-
2
2
was isolated by filtration, washed with n-hexane and dried in
vacuo. Compound 5a was recovered in 43% yield. On the other
hand, the filtrate was concentrated in vacuo, and the residue was
purified by column chromatography (silica gel, benzene:ethyl
acetate = 3:1 v/v) to give 3a (39mg, 35%), 6a (23mg, 15%), 7a
(7mg, 4%), and 4a (21mg, 32%).
ing in benzene-d , characteristic signals due to 8 appeared at 3.86
6
ppm (s, 6H) and at 4.69 ppm (t, 4H, J = 5.8 Hz). However, after
standing for 2 hours, new signals due to the methoxy group of 9
and 10 was observed at 3.81 ppm (s, 3H) and 3.78 ppm (s, 3H),
respectively. These two new singlet signals were identified by
comparison with the signals of authentic samples.
Preparation of 8.
Macrocyclic Compound 5d.
Compound 8 was prepared by a similar method to that described
previously [4] (Scheme 9). Treatment of 6,7-dihydro-2-methyl-
5H-pyrimido[1,2-d][1,2,4]thiadiazole-3(2H)-thione (15) (0.187 g,
1 mmol), which was prepared by thermolysis of 3,4-dimethyl-1,6-
propano-1H,6H-3a-thia(S )-1,3,4,6-tetraaza-thiapentalene-
2,5(3H,4H)-dithione (3: R = H), with p-methoxyphenyl-
Macrocyclic compound 5d was obtained in 17% yield (64
mg) from 3a and 4b by the same procedure as that described in
Method A for 5a. In this reaction, compounds 6d and 7d were
also obtained in 32% (146 mg) and 22% (115 mg) yields,
respectively.
IV
Compound 5d has mp 220-221°(decomp); ir (potassium bro-
mide): 2924, 2853, 1579, 1519, 1480, 1432, 1420, 1342, 1235,
isoselenocyanate (10) [20] (0.212 g, 1 mmol) in CHCl (20 mL)
3
-1
gave unsymmetrical tetraazathiapentalene derivative 16 in 95%
yield (0.38 g). Thermolysis of 16 at 170 °C under reduced pressure
(2mmHg) gave selectively the thiadiazole derivative 9 in 91%
yield (0.273 g). The reaction of 9 with 1.5 equivalents of 10 in
1186, 1156, 1090, 1049, 914, and 720 cm ; uv(CH Cl ) λmax
2
2
1
266 (logε 4.75) nm; H nmr (300 MHz, deuteriochloroform): δ
0.89 (t, 6H, J = 6.7Hz), 1.29-1.58 (m, 28H), 2.28 (br, 2H), 2.59
(br, 4H), 3.48-3.63 (m, 12H), and 4.89-5.00 (m, 4H); FAB-mass
+
refluxing CHCl for 3 hours gave 8 in a 59% yield (0.295 g).
m/z 769 (M+H ).
3
Anal. Calcd. for C
Found: C, 53.23; H, 7.33; N, 14.46.
Compound 6d has mp 119.5-120.5°; ir (potassium bromide):
2957, 2924, 2850, 2185, 2122, 2082, 1582, 1535, 1487, 1341, 1237,
H N S : C, 53.09; H, 7.38; N, 14.57.
34 56 4 3
IV
2-Methyl-3-p-methoxyphenyl-6,7-dihydro-5H-2a-thia(2a-S )-
2,3,4a,7a-tetraazacyclopent[cd]inden-1(2H)-thione-4(3H)-
selenone (16).
Compound 16 has mp 124-126°(decomp); ir (potassium bro-
mide): 3454, 2924, 2832, 2362, 1606, 1568, 1522, 1476, 1372,
1309, 1242, 1210, 1173, 1155, 1121, 1064, 1033, 942, 906, 828,
-1
1192, 1171, 1148, 1135, and 1103 cm ; uv (CH Cl ) λmax 264
2
2
1
(logε 4.54) nm; H nmr (300 MHz, deuteriochloroform): δ 0.89 (t,
3H, J = 6.7Hz), 1.28-1.55 (m, 14H), 2.12-2.36 (m, 3H), 3.28 (s, 3H),
3.52-3.61 (m, 4H), 3.86 (t, 2H, J = 6.1Hz), 4.88-4.93 (m, 2H).
-1
769, 697, and 516 cm ; uv (CH Cl ) λmax 254 (logε 4.60), 290
2
2
1
(logε 4.44), 352 (logε 3.79) nm; H nmr (300 MHz, deuteriochlo-
roform): δ 2.44 (m, 2H), 3.24 (s, 3H), 3.85 (s, 3H), 4.45 (t, 2H,
J = 5.8Hz), 4.66 (t, 2H, J = 5.8Hz), 7.01-7.31 (AA?XX?type,
Anal. Calcd. for C
Found: C, 50.15; H, 6.95; N, 15.15.
Compound 7d has mp 104 -106°; ir (potassium bromide): 2923,
2853, 2189, 2129, 2078, 1584, 1532, 1480, 1420, 1238, 1235,
H N S : C, 49.85; H, 6.83; N, 15.30.
19 31 6 4
+
4H); ms m/z 401 (M+H ).
-1
Anal. Calcd. for C
H N S Se: C, 42.10; H, 4.04; N, 14.03.
1184, 1166, 1146, 1135, and 1080cm ; uv (CH Cl ) λmax 265
14 16 4 2
2
2
1
Found: C, 42.00; H, 4.01; N, 13.89.
(logε 4.54) nm; H nmr (300 MHz, deuteriochloroform): δ 0.89 (t,
3H, J = 6.7Hz), 1.28-1.55 (m, 14H), 2.17-2.35 (m, 5H), 3.53 (dd,
2H), 3.66 (t, 4H, J = 6.1Hz), 3.92 (t, 4H, J = 6.1Hz), 6.41 (dd, 2H).
2-p-Methoxyphenyl-6,7-dihydro-5H-1,2,4-thiadiazolo[4,5-a]-
pyrimidine-3(2H)-selenone (9).
Anal. Calcd. for C
Found: C, 48.93; H, 6.30; N, 15.18.
H N S : C, 48.67; H, 6.31; N, 15.48
22 34 6 5
Compound 9 has mp 94-96°(decomp); ir (potassium bromide):
3480, 1697, 1584, 16519, 1502, 1314, 1252, 1213, 1153, 1062,
1028, 984, 833, 766, and 744 cm ; uv (CH Cl ) λmax 265 (logε
4.01) nm; H nmr (300 MHz, deuteriochloroform): δ 1.89 (m,
2H), 3.61 (t, 2H, J = 5.5Hz), 3.81 (s, 3H), 4.03 (t, 2H, J = 5.8Hz),
6.90 (s, 4H).
Macrocyclic Compound 5b.
-1
2
2
1
Macrocyclic compound 5b was obtained in 46% yield (115
mg) from 3b and 4a by the same procedure as that described in
Method A for 5a. In this reaction, compounds 6b and 7b were

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
199
obtained in 17 % (48 mg) and 4 % (14 mg) yields, respectively.
Compound 5b has mp 233-235° (decomp); ir (potassium bro-
mide): 2919, 2851, 1575, 1531, 1478, 1416, 1236, 1198, 1162,
Method B for 5a. Compound 5e was obtained as a yellow solid,
mp 195-197°; ir (potassium bromide): 3065, 3030, 2934, 2856,
1578, 1527, 1475, 1458, 1403, 1364, 1320, 1273, 1235, 1188,
-1
-1
1143, 1111, and 753 cm ; uv(CH Cl ) λmax 266 (logε 4.76) nm;
1111, 932, 823, 756, and 696 cm ; uv (CH Cl ) λmax 401 (logε
2
2
2
2
1
1
H nmr (300 MHz, deuteriochloroform): δ 0.88 (t, 6H, J =
4.72), 380 (logε 4.72), 360 (logε 4.56), 258 (logε 5.60) nm; H
nmr (300 MHz, deuteriochloroform): δ 1.27 (m, 4H), 1.54-1.72
(m, 8H), 2.20 (m, 2H), 3.48 (m, 4H+4H), 4.51 (s, 4H), 4.73 (d,
2H, J = 14.5Hz), 4.99 (d, 2H, 18.1Hz), 5.96 (d, 8H), 7.29 (m,
10H), 7.64 (m, 8H), 8.45 (m, 8H).
6.7Hz), 1.27-1.51 (m, 44H), 2.15 (m, 2H), 3.47 (dd, 4H), 4.90
(dd, 4H), 5.00 (s, 8H), 7.29 (s, 8H).
Anal. Calcd for C
H N S : C, 59.15; H, 6.77; N, 12.54.
52 76 8 6
Found: C, 59.32; H, 6.52; N, 12.55.
Compound 6b has mp 224 – 225.5°(decomp); ir (potassium
bromide): 2919, 2849, 2150, 2076, 1583, 1531, 1482, 1470,
Anal. Calcd. for C
Found: C, 66.37; H, 5.53; N, 9.53.
H O N S : C, 66.41; H, 5.40; N, 9.39.
66 64 2 8 6
-1
1416, 1400, 1332, 1239, 1204, 1189, 1149, 1107, and 718 cm ;
Macrocyclic Compound 5f.
1
uv (CH Cl ) λmax 264 (logε 4.54) nm; H nmr (300 MHz, deu-
2
2
teriochloroform): δ 0.88 (t, 3H, J = 6.7Hz), 1.27-1.54 (m, 22H),
2.23 (m, 1H), 3.19 (s, 3H), 3.51-3.61 (m, 2H), 4.69 (s, 2H), 4.85-
4.96 (m, 4H), and 7.27-7.42 (m, 4H).
Macrocyclic compound 5f was obtained in 30% yield (56 mg)
from 3d and 4d by the same procedure as that described in
Method B for 5a. Compound 5f has mp 195-197° (decomp); ir
(potassium bromide): 2913, 2853, 1577, 1526, 1473, 1400, 1355,
Anal. Calcd for C
H N S : C, 58.39; H, 7.18; N, 12.16.
28 41 5 4
-1
Found: C, 58.69; H, 7.11; N, 11.87.
Compound 7b has mp 204 – 207°(decomp); ir (potassium
bromide): 2922, 2852, 2174, 2088, 1582, 1531, 1469, 1421,
1307, 1283, 1234, 1157, 1094, 996, 952, 737, 698, and 670 cm ;
1
H nmr (300MHz, deuteriochloroform): δ 1.52 (m, 12H), 2.22
(m, 2H), 3.49 (m, 4H+4H), 4.01 (m, 8H), 4.19 (m, 8H), 4.50 (s,
4H), 4.79 (br, 2H), 7.36 (m, 18H).
-1
1337, 1236, 1165, 1144, 753, and 668 cm ; uv (CH Cl ) λmax
2
2
1
265 (logε 4.53) nm; H nmr (300 MHz, deuteriochloroform): δ
0.88 (t, 3H, J = 6.7Hz), 1.26-1.53 (m, 22H), 2.22 (m, 1H), 3.52
(dd, 2H), 4.71 (s, 4H), 4.88 (s, 4H), 4.93 (dd, 2H), and 7.26-
7.36 (m, 8H).
Anal. Calcd. for C
H O N S : C, 54.39; H, 6.30; N, 15.10.
42 58 2 10 6
Found: C, 54.41; H, 6.42; N, 14.95.
Macrocyclic Compound 5g.
Anal. Calcd for C
Found: C, 59.78; H, 6.44; N, 11.32.
H N S : C, 59.79; H, 6.41; N, 11.62.
Macrocyclic compound 5g was obtained in 90% yield (197
mg) from 3d and 4a by the same procedure as that described in
Method B for 5a. Compound 5g has mp 215-216° (decomp); ir
(potassium bromide): 2916, 2857, 1572, 1524, 1474, 1419, 1235,
1163, 1140, 814, 751, and 683 cm ; H nmr (300 MHz, deuterio-
chloroform): δ 1.27 (m, 4H), 1.54-1.72 (m, 8H), 2.16 (m, 2H),
36 46 6 6
Macrocyclic Compound 5c.
-1 1
Macrocyclic compound 5c was obtained in 39% yield (114 mg)
from 3c and 4a by the same procedure as that described in Method
A for 5a. In this reaction, compounds 6c and 7c were obtained in
16% (52 mg) and 3% (13 mg) yields, respectively; mp 218-
219°(decomp); ir (potassium bromide): 2921, 2851, 1576, 1532,
1478, 1417, 1236, 1198, 1165, 1144, and 753 cm ; uv (CH Cl )
λmax 266 (logε 4.66) nm; H nmr (300 MHz, deuteriochloroform):
δ 0.88 (t, 6H, J = 6.7Hz), 1.26-1.52 (m, 68H), 2.17 (m, 2H), 3.47
(dd, 4H), 4.90 (dd, 4H), 5.00 (s, 8H), and 7.29 (s, 8H).
Anal. Calcd for C
Found: C, 65.22; H, 8.88; N, 9.25.
3.47 (m, 4H+4H), 4.49 (s, 4H), 4.99 (d, 4H, J = 2.4Hz), 5.14 (s,
+
8H), 7.29 (m, 18H); FAB-mass m/z 993(M+H ).
Anal. Calcd. for C O N S : C, 60.45; H, 5.68; N, 11.28.
H
50 56
2 8 6
-1
2
2
Found: C, 60.75; H, 5.70; N, 10.98.
1
Macrocyclic Compound 5h.
Macrocyclic compound 5h was obtained in a 67% yield (133
mg) from 3d and 4e by the same procedure as that described in
Method B for 5a. Compound 5h has mp 228-230° (decomp); ir
(potassium bromide): 2929, 2854, 1576, 1515, 1457, 1340, 1231,
H
N S : C, 65.48; H, 8.59; N, 9.55.
64 100 8 6
Compound 6c has mp 123-124°; ir (potassium bromide): 2918,
2849, 2151, 2077, 1583, 1531, 1482, 1471, 1416, 1400, 1342,
-1 1
1184, 1162, 1129, 809, 776, 745, 697, and 670 cm ; H nmr (300
-1
1234, 1203, 1189, 1149, 1111, and 718 cm ; uv (CH Cl ) λmax
MHz, deuteriochloroform): δ 1.25 (m, 4H), 1.61 (m, 8H), 2.22
(m, 2H), 3.48 (m, 4H+4H), 4.50 (s, 4H), 4.96 (d, 4H, J = 13.4Hz),
5.29 (s, 8H), 7.34 (m, 18H).
2
2
1
264 (logε 4.54) nm; H nmr (300 MHz, deuteriochloroform): δ
0.88 (t, 3H, J = 6.7Hz), 1.26-1.54 (m, 34H), 2.23 (m, 1H), 3.18(s,
3H), 3.51-3.61 (m, 2H), 4.69 (s, 2H), 4.85-4.96 (m, 4H), and
7.27-7.41 (m, 4H).
Anal. Calcd. for C
H O N S : C, 60.45; H, 5.68; N, 11.28.
50 56 2 8 6
Found: C, 60.71; H, 5.77; N, 11.31.
Anal. Calcd for C
Found: C, 62.01; H, 8.01; N, 10.40.
H N S : C, 61.87; H, 8.09; N, 10.61.
34 53 5 4
Macrocyclic Compound 5i.
Compound 7c has mp 205-210° (decomp) ; ir (potassium bro-
mide): 2928, 2854, 2175, 2100, 1586, 1524, 1472, 1421, 1334,
Macrocyclic compound 5i was obtained in 13% yield (5 mg)
from 3f and 4a by the same procedure to that described by
Method B for 5a. Compound 5i was obtained as a Yellow solid,
mp 253-255° (decomp); ir (potassium bromide): 2909, 2856,
1685, 1654, 1637, 1577, 1542, 1523, 1458, 1420, 1343, 1154,
-1
1236, 1169, 1144, 755, 721, and 669 cm ; uv (CH Cl ) λmax
2
2
1
266 (logε 4.55) nm ; H nmr (300 MHz, deuteriochloroform): δ
0.88 (t, 3H, J = 6.7Hz), 1.27-1.53 (m, 34H), 2.22 (m, 1H),3.52(dd,
2H), 4.71 (s, 4H), 4.87-4.96 (m, 6H), and 7.26-7.35 (m, 8H).
-1
1117, 901, 736, and 675 cm ; uv (CH Cl ) λmax 389 (logε
2
2
1
4.35), 368 (logε 4.56), 358 (logε 4.25), 257 (logε 5.52) nm; H
nmr (300 MHz, deuteriochloroform): δ 2.10 (m, 2H), 3.42 (m,
4H), 3.57 (m, 4H), 4.66 (m, 4H), 4.87 (s, 8H), 7.19 (m, 8H), 7.62
(m, 10H), 8.01 (br, 8H).
Anal. Calcd. for C
H N S : C, 62.49; H, 7.24; N, 10.41.
42 58 6 5
Found: C, 62.61; H, 7.40; N, 10.24.
Macrocyclic Compound 5e.
Macrocyclic compound 5e was obtained in 43% yield (51 mg)
from 3d and 4c by the same procedure as that described in
Anal. Calcd. for C H N S : C, 66.38; H, 4.61; N, 10.68.
Found: C, 66.21; H, 4.51; N, 10.89.
58 48 8 6

200
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
Macrocyclic Compound 11a.
1.54-1.72 (m, 8H), 2.03 (m, 2H), 3.47 (m, 8H), 4.43 (s, 4H), 4.99
(m, 8H), 7.28 (m, 4H), 7.31 (m, 18H); FAB-mass m/z 937
(M+H ).
A mixture of 5a (179mg, 0.2mmol) and NaBH (152mg,
4.0mmol) in DMSO (20 mL) was stirred at room tempareture for
24 hours, quenched with an aqueous NH Cl solution, and then
4
+
Anal. Calcd. for C
H N O S : C, 64.07; H, 6.88; N, 11.95.
50 64 8 2 4
4
Found: C, 63.86; H, 7.03; N, 12.00.
extracted with CH Cl . The extract was washed with water,
2
2
dried (Na SO ) and concentrated. The crude product was puri-
Macrocyclic Compound 11h.
2
4
fied by column chromatography (silica gel, CH Cl :ethylacetate
2
2
Macrocyclic compound 11h was obtained in 64% yield (31
mg) from 5h by the same procedure as that described for 11a.
Compound 11h has mp 214-215° (decomp); ir (potassium bro-
mide): 3230, 3039, 2924, 2856, 1527, 1490, 1457, 1375, 1324,
= 19:1) to give 11a (111mg, 66%) as white solid, mp 210-211°
(decomp); ir (potassium bromide): 3216, 3049, 2924, 2854,
1560, 1537, 1488, 1418, 1382, 1337, 1308, 1259, 1171, 1140,
-1
1094, 961, 933, 901, 878, 827, and 754 cm ; uv (CH Cl ) λmax
2
2
-1
1
1091, 873, 741, and 696 cm ; H nmr (300 MHz, dimethylsul-
1
257 (logε 4.70) nm; H nmr (300 MHz, acetone-d ): δ 0.86 (t,
6
foxide-d ): δ 1.21 (m, 4H), 1.33-1.52 (m, 8H), 1.81 (m, 2H), 3.40
6
6H, J = 6.7Hz), 1.22-1.28 (m, 28H), 1.73 (m, 2H), 3.40-3.81 (br,
4H), 4.26-4.65 (br, 4H), 4.93 (br, 4H+8H), 7.26 (s, 8H), 8.64 (br,
(m, 8H), 4.42 (s, 4H), 4.73 (m, 8H), 5.09 (s, 8H), 7.29 (m, 18H),
8.53 (br, 4H).
+
4H); FAB-mass m/z 838 (M+H ).
Anal. Calcd. for C
H N O S : C, 64.07; H, 6.88; N, 11.95.
50 64 8 2 4
Anal. Calcd. for C
H N S : C, 63.11; H, 8.19; N, 13.38.
44 68 8 4
Found: C, 64.26; H, 6.59; N, 11.68.
Found: C, 63.25; H, 8.19; N, 13.15.
Alkaline Hydrolysis of 3a.
Macrocyclic Compound 11b.
An aqueous KOH solution (KOH 0.41 g/H O 5 mL) was added
2
Macrocyclic compound 11b was obtained in 46% yield (44 mg)
from 5b by the same procedure as that described for 11a.
Compound 11b has mp 134-135° (decomp); ir (potassium bro-
to an ethanol solution (45 mL) of 3a (149 mg, 0.40 mmol). The
mixture was stirred at room temperature for 40 minutes, and then
neutralized with diluted HCl solution. The reaction mixture was
concentrated and extracted with CH Cl . The extract was washed
mide): 3210, 3046, 2924, 2853, 1561, 1535, 1488, 1466, 1407,
-1
2
2
1381, 1336, 1282, 1240, 1172, and 1092 cm ; uv (CH Cl ) λmax
2
2
with water, dried (Na SO ), and concentrated. The crude product
1
2
4
258 (logε 4.66) nm; H nmr (300 MHz, acetone-d ): δ 0.88 (t, 6H,
6
was purified by column chromatography (silica gel, toluene : ethyl-
acetate = 4 :1) to give 13 (37 mg, 28%) and 12 (53 mg, 37%).
J = 6.4Hz), 1.22-1.27 (m, 44H), 1.73 (m, 2H), 3.40-3.82 (br, 4H),
4.26-4.62 (br, 4H), 4.93 (br, 4H+8H), 7.26 (s, 8H), 8.64 (br, 4H).
Anal. Calcd. for C
Found: C, 65.48; H, 12.08; N, 9.16.
H N S : C, 65.77; H, 11.80; N, 8.92.
1-Methyl-3-{2-[(3-methyl-thioureido)-methyl]-decyl}-
thiourea(12).
52 84 8 4
Macrocyclic Compound 11e.
Compound 12 was obtained as an oil; ir (potassium bromide):
3252, 2926, 2854, 1650, 1538, 1469, 1392, 1216, 1167, 1040, 741,
713, and 668 cm ; H nmr (300 MHz, deuteriochloroform): δ 0.88
(t, 3H, J = 6.7Hz), 1.27-1.41 (m, 14H), 2.00 (m, 1H), 3.19 (d, 6H,
J = 4.3Hz), 3.57-3.66 (m, 2H), 4.73-4.79 (m, 2H), 10.65 (br, 2H).
Macrocyclic compound 11e was obtained in 53% yield (9 mg)
as yellow solid from 5e by the same procedure as that described
for 11a. Compound 11e has mp 188-190° (decomp); ir (potassium
-1 1
-1
bromide): 2925, 2857, 1654, 1542, 1458, 1284, and 695 cm ; uv
1
Anal. Calcd for C
H N OS : C, 54.17; H, 9.25; N, 16.85.
(CH Cl ) λmax 255 (logε 4.65) nm; H nmr (300 MHz, acetone-
15 32 4 2
2
2
Found: C, 53.98; H, 9.34; N, 17.02.
d ): δ 1.29 (m, 4H), 1.43 (br, 4H), 1.60 (br, 4H), 2.25 (m, 2H),
6
3.45 (m, 8H), 4.48 (m, 8H), 5.69 (m, 4H+8H), 7.35 (br, 10H), 7.51
(br, 4H), 7.93 (m, 8H), 8.30 (m, 8H).
5-Octyl-2-oxo-dihydro-pyrimidine-1, 3-dicarbothioic Acid bis-
methylamide (13).
Anal. Calcd. for C
H N O S : C, 69.68; H, 6.38; N, 9.85.
66 72 8 2 4
Compound 13 was obtained as an oil; ir (potassium bromide):
Found: C, 69.39; H, 6.68; N, 10.11.
3263, 3071, 2923, 2857, 1556, 1462, 1347, 1291, 1211, 1056, and
Macrocyclic Compound 11f.
-1 1
666 cm ; H nmr (300 MHz, deuteriochloroform): δ 0.88 (t, 3H, J =
6.7Hz), 1.27-1.39 (m, 14H), 1.97 (m, 1H), 2.98 (d, 6H, J = 3.1Hz),
3.36-3.45 (m, 2H), 3.84 (br, 2H), 6.40 (br, 2H), 6.91 (br, 2H).
Macrocyclic compound 11f was obtained in 35% yield (6 mg)
from 5f by the same procedure as that described for 11a.
Compound 11f has mp 168-170° (decomp); ir (potassium bro-
Anal. Calcd for C
H N OS : C, 53.59; H, 8.43; N, 15.62.
16 30 4 2
-1
mide): 2935, 2857, 1654, 1560, 1542, 1262, 1117, and 803 cm ;
Found: C, 53.29; H, 8.43; N, 15.32.
1
uv (CH Cl ) λmax 257 (logε 4.70) nm; H nmr (300 MHz, ace-
2
2
Alkaline Hydrolysis of 13.
tone-d ): δ 1.29 (m, 4H), 1.41 (br, 4H), 1.59 (br, 4H), 2.25 (m,
6
An aqueous KOH solution (KOH 0.41 g/H O 5 mL) was
2H), 2.58 (br, 2H), 3.47 (m, 8H), 3.62 (m, 8H), 4.20 (m, 16H),
4.48 (s, 4H), 4.74 (br, 4H), 5.33 (m, 4H), 7.35 (m, 10H).
2
added to an ethanol solution (45 mL) of 13 (53 mg, 0.15 mmol).
The reaction mixture was refluxed for 5 minutes, cooled to room
temperature, and then neutralized with diluted HCl solution. The
Anal. Calcd. for C
H N O S : C, 57.90; H, 6.85; N, 16.07.
42 66 10 2 4
Found: C, 58.15; H, 6.47; N, 15.98.
mixture was concentrated and extracted with CH Cl . The
2
2
Macrocyclic Compound 11g.
extract was washed with water, dried (Na SO ) and concentrated.
2
4
Macrocyclic compound 11g was obtained in 37% yield (35
mg) from 5g by the same procedure as that described for 11a.
Compound 11g has mp 223-225° (decomp); ir (potassium bro-
The crude product was purified by column chromatography (sil-
ica gel, toluene : ethylacetate = 1:3) to give 17 (34mg, 69%).
Macrocyclic Compound 14a.
mide): 3056, 2926, 2857, 1637, 1542, 1284, 1102, 970, 740, and
-1
699 cm ; uv (CH Cl ) λmax 328 (logε 5.62), 275 (logε 5.08)
An aqueous KOH solution (KOH 2.0 g/H O 25 mL ) was
2
2
2
1
nm; H nmr (300 MHz, deuteriochloroform): δ 1.25 (m, 4H),
added to an ethanol solution (60 mL) of 5a (125 mg, 0.14mmol).

Jan-Feb 2002
Synthesis and Properties of Novel Macrocyclic Compounds
201
The reaction mixture was refluxed for 4 hours, cooled to room
tempareture, and then neutralized with diluted HCl solution. The
mixture was concentrated and extracted with CH Cl . The
4H), 4.59 (br, 8H), 7.15-7.37 (m, 18H), 7.46 (br, 4H), 7.83 (br,
4H); FAB-mass m/z 913 (M+H ).
+
Anal. Calcd. for C
H N O S : C, 63.12; H, 7.06; N, 12.27.
2
2
48 64 8 2 4
extract was washed with water, dried (Na SO ) and concen-
Found: C, 62.88; H, 7.10; N, 12.42.
2
4
trated. The crude product was purified by column chromatogra-
phy (silica gel, CH Cl :ethylacetate = 3:1) to give 14a (50 mg,
Acknowledgments.
2
2
44%) as a colorless solid, mp 199-200°(decomp); ir (potassium
bromide): 3299, 3057, 2923, 2852, 1557, 1467, 1412, 1383,
This work was supported by a Grant-in Aid for Scientific
Research from the Ministry of Education, Science, Sports and
Culture of Japan, to which the authors wish to express their grate-
ful acknowledgments.
-1
1337, 1291, 1223, 970, 687, and 601 cm ; uv (methanol) λmax
1
244 (logε 4.77) nm; H nmr (300 MHz, methanol-d ): δ 0.89 (t,
4
6H, J = 6.7Hz), 1.25-1.30 (m, 28H), 1.90 (m, 2H), 3.56 (m, 4H),
4.59 (m, 8H), 7.24 (s, 8H), {4H signal was overlapped with
REFERENCES AND NOTES
+
methanol's one.}; FAB-mass m/z 814 (M+H ).
Anal. Calcd. for C
Found: C, 61.75; H, 8.52; N, 13.59.
H N S : C, 62.02; H, 8.43; N, 13.78.
42 68 8 4
[1a] F. Arndt, P. Nachtwey, J. Pusch, Chem. Ber., 58, 1633 (1925);
[b] S. Bezzi, M. Mammi, C. Carbuglio, Nature (London), 182, 247
(1958); [c] G. Pfister-Guillouzo, Bull. Soc. Chim. Fr., 1316 (1958).
[2a] E. Klingsberg, J. Org. Chem., 33, 2915 (1968); [b] J.-L.
Derocque, M. Perrier and J. Vialle, Bull. Soc. Chim. Fr., 2062 (1968); [c]
D. H. Reid and J. D. Symon, J. Chem. Soc., Chem. Commun. 1314 (1969);
[d] N. Lozac'h, Adv. Heterocycl. Chem., 13, 161 (1971); [e] D. H. Reid, J.
Chem. Soc., 3187 (1971); [f] D. H. Reid and R. G. Webster, J. Chem. Soc.,
1283 (1972); [g] R. J. S. Beer and A. Waylor, Tetrahedron Lett., 2989
(1973); [h] A. S. Ingram, D. H. Reid and J. D. Symon, J. Chem. Soc.,
Perkin Trans. 1, 242 (1974); [i] R. Gleiter, and R. Gygax, Top Curr. Chem.,
86, 139 (1976); [j] J. Goerdeler, H. Hohage, and I. Zeid, Chem. Ber., 109,
3108 (1976); [k] R. Gleiter and J. Spanget-Larsen, Top. Curr. Chem., 86,
139 (1979); [l] Y. Yamamoto and K. Akiba, Heterocycles, 13, 297 (1979);
[m] M. Yokoyama, T. Shiraishi, H. Hatanaka and K. Ogata, J. Chem. Soc.,
Chem. Commun., 1704 (1985); [n] J. P. Michael, D. H. Reid, B. G. Rose
and R. A. Speirs, J. Chem. Soc., Chem. Commun., 1494 (1988).
[3a] J. I. Musher, Angew. Chem., Int. Ed. Engl., 8, 54 (1969); [b] F.
Iwasaki and K. Akiba, Bull. Chem. Soc. Jpn., 57, 2581 (1984); [c] K.
Akiba, K. Kashiwagi, Y. Ohyama, Y. Yamamoto and K. Ohkata, J. Am.
Chem. Soc., 107, 2721 (1985); [d] R. A. Hayes, and J. C. Martin, In
Organic Sulfur Chemistry: Theoretical and Experimental Advances; F.
Bemardi, I. G. Csizmadia and A. Mangini, Eds.; Elsevier Scientific
Publishing : Amsterdam, pp 408 (1985); [e] A. Kucsman, and I. Kapovits,
In Organic Sulfur Chemistry; Theoretical and Experimental Advances; F.
Bemardi, I. G. Csizmadia, and A. Mangini, Eds.; Elsevier scientific
Publishing : Amsterdam, pp 191 (1985); [f] K. Akiba, M. Ohsugi, H.
Iwasaki, and K. Ohkata, J. Am. Chem. Soc., 110, 5576 (1988).
[4] N. Matsumura, M. Tomura, O. Mori, Y. Tsuchiya, S. Yoneda
and K. Toriumi, Bull. Chem. Soc. Jpn., 61, 2419 (1988).
Macrocyclic Compound 14e.
Macrocyclic compound 14e was obtained in 44% yield (50 mg)
from 5e by the same procedure as that described for 14a.
Compound 14e was obtained as a yellow solid; mp 180-
182°(decomp); ir (potassium bromide): 2926, 2849, 1658, 1560,
-1
1542, 1508, 1458, 1282, 1117, 1002, 745, and 701 cm ; uv
1
(CH Cl ) λmax 369 (logε 3.78), 252 (logε 5.33) nm; H nmr (300
2
2
MHz, acetone-d ): δ 1.29 (m, 4H), 1.43 (m, 4H), 1.59 (m, 4H),
6
2.25 (m, 2H), 3.48 (m, 8H), 4.38 (s, 4H), 4.48 (m, 12H), 7.33 (m,
10H), 7.65 (br, 2H), 7.87 (br, 2H), 7.94 (m, 8H), 8.28 (m, 8H).
Anal. Calcd. for C
H N O S : C, 69.03; H, 6.52; N, 10.06.
64 72 8 2 4
Found: C, 68.88; H, 6.35; N, 9.89.
Macrocyclic Compound 14f.
Macrocyclic compound 14f was obtained in 83% yield (14
mg) from 5f by the same procedure as that described for 14a.
Compound 14f was obtained as a yellow solid; mp 159-
161°(decomp); ir (potassium bromide): 3238, 2929, 2849, 1685,
1654, 1560, 1457, 1369, 1273, 1205, 1117, 741, 698, and 658
-1
1
cm ; H nmr (300 MHz, acetone-d ): δ 1.29 (m, 4H), 1.46 (m,
6
4H), 1.59 (m, 4H), 1.89 (m, 2H), 2.96 (br, 4H), 3.33 (m, 8H), 3.48
(m, 8H), 3.75 (m, 16H), 4.48 (s, 4H), 5.60 (m, 4H), 7.13 (br, 2H),
7.23 (br, 2H), 7.35 (m, 10H).
Anal. Calcd. for C
H N O S : C, 57.89; H, 6.85; N, 16.07.
42 66 10 2 4
Found: C, 57.59; H, 6.98; N, 15.79.
[5a] N. Matsumura, M. Tomura, M. Yoneda and K. Toriumi,
Chem. Lett., 1047 (1986); [b] N. Matsumura, M. Tomura, O. Mori, Y.
Tsuchiya and S. Yoneda, Bull. Chem. Soc. Jpn., 61, 2419 (1988); [c] N.
Matsumura, M. Tomura, O. Mori, Y. Takamura and S. Yoneda,
Tetrahedron Lett., 30, 2259 (1989); [d] M. Tomura, M. Chikusa, K. Inazu,
A. Ito, N. Matsumura and H. Inoue, Synthesis, 457 (1991) and references
cited therein.
[6] N. Matsumura, M. Tomura, O. Mori, M. Ukawa and S.
Yoneda, Heterocycles, 26, 3097 (1987).
[7a] N. Matsumura, O. Mori, M. Tomura and S. Yoneda, Chem.
Lett., 2259 (1989); [b] M. Tomura, O. Mori, N. Matsumura, and H.
Inoue, J. Heterocycl. Chem., 28, 221 (1991).
Macrocyclic Compound 14g.
Macrocyclic compound 14g was obtained in 52% yield (38 mg)
from 5g by the same procedure as that described for 14a.
Compound 14g has mp 216-217° (decomp); ir (potassium bro-
mide): 3258, 3033, 2924, 2849, 1560, 1283, 1100, and 698 cm ; H
nmr (300 MHz, deuteriochloroform): δ 1.22 (m, 4H), 1.46 (m, 8H),
-1 1
1.97 (m, 2H), 3.36 (m, 8H), 4.41 (s, 4H), 4.89 (m, 8H), 5.14 (s, 8H),
7.19 (br, 4H), 7.24 (m, 10H); FAB-mass m/z 913 (M+H ).
+
Anal. Calcd. for C
H N O S : C, 63.12; H, 7.06; N, 12.27.
48 64 8 2 4
Found: C, 62.88; H, 7.10; N, 12.42.
[8] N. Matsumura, R. Hirase and H. Inoue, Tetrahedron Lett., 35,
899 (1994) and references cited therein.
Macrocyclic Compound 14h.
[9] F. G. Bordwell, D. J. Algrim and J. A. Harrelson Jr., J. Am.
Chem. Soc., 110, 5904 (1988).
[10] For substituent effects on association constants of arylth-
ioureas: C. S. Wilcox, D. Kim, L. H. Romano, A. L. Kuo and D. P.
Curran, Tetrahedron, 51, 621 (1995).
Macrocyclic compound 14h was obtained in 26% yield (12
mg) from 5h by the same procedure as that described for 14a.
Compound 14h has mp 211-213° (decomp); ir (potassium bro-
mide): 3362, 3299, 3057, 2923, 2852, 1557, 1467, 1412, 1383,
1337, 1291, 1223, 970, 687, and 601 cm ; H nmr (300 MHz,
deuteriochloroform): δ 1.23 (m, 4H), 1.36-1.52 (m, 8H), 1.84 (m,
2H), 2.74 (t, 4H), 3.15 (d, 4H, J = 12.4Hz), 3.41 (t, 4H), 4.41 (s,
-1
1
[11] P. Buhlmann, S. Nishizawa, K. P. Xiao and Y. Umezawa,
Tetrahedron, 53, 1647 (1997).
[12a] T. Shioya, S. Nishizawa and N. Teramae, J. Am. Chem. Soc.,

202
N. Matsumura, T. Konishi, H. Hayashi, M. Yasui, F. Iwasaki, and K. Mizuno
Vol. 39
120, 11534 (1998); [b] Y. Tobe, S. Sasaki, M. Mizuno, K. Hirose and K.
Naemura, J. Org. Chem., 63, 7481 (1998).
[13] Preliminaly communication: N. Matsumura, T. Konishi, H.
Hayashi, M. Yasui, F. Iwasaki and K. Mizuno, Heterocycles, 53, 1239
(2000).
terminal three atoms of alkyl chain and solvent molecules are disordered,
so that R factors were not sufficiently reduced. The backbone structure,
however, was obtained from the direct method followed by successive
Fourier syntheses.
[15] Johnson C. K., ORTEPII, Report OLNL-5138, Oak Ridge
National Laboratory, Oak Ridge, TN, 1976.
[14] X-ray Crystallography. Crystallographic data of 11a.
C
H
N S + 2.14CHCl , trigonal, space group R3(hexagonal setting),
[16] T. Shibanuma, M. Shiono, andT. Mukaiyama, Chem. Lett.,
573 (1977).
[17] G. R. Newkome, D. K. Kohli and F. R. Fronczek, J. Am.
Chem. Soc., 104, 994 (1982).
44 68
8
4
3
3
a = 30.380(8), c = 16.704(5) Å, V = 13351(5) Å , Z = 9, d
cm . A colorless crystal with dimensions of 0.2x0.3x0.2 mm was sealed
in a glass capillary immersed in a minimum amount of solvent soon after
= 1.223g
calc
-3
picked up from the CHCl /hexane solution, because the crystals were
[18] H. Shirai, Y. Takahashi, H. Tsutsumi, A. Kurose, K. Hanabusa
and N. Hozyo, Japan Kokai, 51645 (1987).
[19] Organic Synthesis, Coll. Vol. 3, 394.
[20] p-Methoxyphenyl isoselenocyanate was prepared by a similar
method to that in literature [21].
3
immediately deteriorated in the air. The specimen was cooled at 253 K
during the data collection to reduce the deterioration. The intensity data
were collected on a MAC Sceience DIP-3000 diffractometer using the
imaging plate as a detector with Mo-Kα radiation. Whole data were col-
lected within about 12 hours. 11828 reflections measured, 6715 unique,
[21] M. Segi and T. Nakajima, Yukigosei Kagaku Kyokaishi, 53,
678 (1995).
1760 with Fo > 2.5σ(F), R = 0.148, Rw = 0.393 (315 variables). The
2