Synthesis of heterocyclic systems by the reaction of zwitterionic compounds with isocyanates and thiophosgene

Article abstract of DOI:10.1055/s-2002-34866

The reaction of various isocyanates or thiophosgene with zwitterionic pyrimidinylium and 1,3-diazepinylium derivatives has led to the formation of unusually substituted [1,3]oxazolo[3,4-a]pyrimidines and novel heterocyclic system such as [1,3]oxazolo[3,4-

Full text of DOI:10.1055/s-2002-34866

LETTER
1831
Synthesis of Heterocyclic Systems by the Reaction of Zwitterionic Compounds
with Isocyanates and Thiophosgene
Synthesis of
H
ete
a
rocyclic Sy
r
stems bara Zaleska,* Marcin Karelus
Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland
Fax +48(12)6340515; E-mail: zaleska@chemia.uj.edu.pl
Received 13 September 2002
esting systems: 1,3-oxazolo[3,4-a]pyrimidines and novel
1,3-oxazolo[3,4-a][1,3]diazepines.
Abstract: The reaction of various isocyanates or thiophosgene with
zwitterionic pyrimidinylium and 1,3-diazepinylium derivatives
has led to the formation of unusually substituted [1,3]oxazolo[3,4-
a]pyrimidines and novel heterocyclic system such as [1,3]oxazo-
lo[3,4-a][1,3]diazepine.
At the center of our investigation lie 2-anilino-2-methoxy-
3-oxothiobutanoic acid anilides 1, which are readily
prepared9 from 3-oxothiobutanoic acid anilides by the one
pot, tandem condensation-addition reaction with ni-
trosobenzene. The multifunctional compounds 1 have a
high synthetic potential.
Key words: zwitterionic compounds, fused heterocycles, oxazoli-
dine, pyrimidine, 1,3-diazepine
In a recent paper10 we have described the heterocycliza-
tion (at C2) of 2-anilino-2-ethoxy-3-oxothiobutanoic acid
anilides 1 with aliphatic 1,3- and 1,4-diamines leading to
novel zwitterionic compounds 2 and 3,11 respectively.
Good leaving groups at C2 of compounds 1 facilitate cy-
clization followed by a novel rearrangement of 3-
oxothiobutanoic acid anilides 1 to 2-hydroxythiopropano-
ic acid zwitterionic derivatives 2 and 3 (Scheme 1). We
now wish to report the application of zwitterionic com-
pounds 2 and 3 in the synthesis of saturated fused hetero-
cyclic systems.
Oxazolopyrimidine or 1,3-oxazolo[1,4]diazepine moi-
eties are essential in many pharmacologically relevant
compounds. Derivatives of 1,3-oxazolo[3,4-a]pyrimi-
dine, such as 2,4-diaza-4-deoxypodophyllotoxin, show
significant activity against vincristine-resitant P-388 leu-
kemia,1 whereas 1,3-oxazolo[3,2-c]pyrimidine deriva-
tives have anti-inflammatory properties.2 Biological
activity of compounds based on the 1,3-oxazolo[3,2-a]py-
rimidine moiety is considered to be very significant.3
Moreover, some derivatives of this system have technical
applications4 in the chemistry of polymers. Some 1,3-ox-
azolo[3,4-d][1,4]diazepine derivatives have antibacterial
activity5–7 whereas in commercially available drugs, such
as mexazolam or oxazolam, the 1,3-oxazolo[3,2-
d][1,4]diazepine moiety is present.8 In this regard, we
have now synthesized a series of pharmacologically inter-
Treatment of compound 2 or 3 with 2 equivalents of phe-
nyl isocyanate in toluene (100 °C) for 15 minutes fur-
nished a mixture of compounds 4 or 5, respectively,12 with
an equivalent amount of N,N -diphenylurea (Scheme 1).
HN
NH
R-HN
NH2(CH2)3NH2
toluene / 75 °C
N
N
O
O
+
H3C
OH
S
H3C
R-HN
O
Ar-HN-SC
Ar-N
Me-O
H3C
NH-Ph
NH-Ar
R-N=C=O
2 a, b
4 a, b
R = Ph, naphthyl,
p-chlorophenyl,
cyclohexyl
1a Ar = C6H5
1b Ar = C6H4Cl-p
O
S
R-HN
R-HN
HN
NH
N
N
O
+
O
NH2(CH2)4NH2
toluene / 75 °C
H3C
OH
S
H3C
O
Ar-HN-SC
Ar-N
3 a, b
5 a, b
Scheme 1
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1831,1834,ftx,en;D15202ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1832
B. Zaleska, M. Karelus
LETTER
When various isocyanates were used, the same final prod-
= 7.55–10.00 ppm, characteristic for zwitterionic
H
uct 4 or 5 was isolated, as well as the appropriate ureas. In compounds 2 and 3, is not present but at 10.55–11.68 ppm
terms of a mechanism for this process, the oxygen of the a singlet corresponding to the thioanilide NH group is
hydroxyl group of the lactic acid derivatives 2 or 3 readily observed. A resonance in the 13C NMR spectra of 4–7 at
reacts with the electrophilic carbon of the isocyanate
C = 192.2–194.1 ppm is consistent with the C=S of thio-
group. Subsequently, 1,3-oxazolidine oxidative ring clo- anilide group. The C=O group of compounds 4 and 5 is
sure takes place with elimination of an amine derived present at approx. 154 ppm, while the C=S group of com-
from the isocyanates. Treatment of compounds 2 and 3 pounds 6 and 7 appears in the range 184.9–187.7 ppm.
with two equivalents of isocyanate, allows quantitative The presence of a carbonyl group situated between oxy-
formation of the appropriate symmetrical ureas.
gen and nitrogen in heterocyclic systems 4 and 5, charac-
teristic for the fused systems, is observed at around 1800
cm–1 in the IR spectra, as well as C-O group of the cyclic
ester at around 1080 cm–1. On the other hand the thioam-
ide N-H band appeared at around 3180 cm–1.
Analogues 6 and 7, possessing a thiocarbonyl group, were
obtained13 using thiophosgene in a two phase system
(chloroform/water) with sodium bicarbonate (Scheme 2).
Reactions were carried out at 0 °C for 40 minutes with 1
equivalent of thiophosgene and 2 equivalents of base. The In summary, we have demonstrated the utility, of the re-
compounds 6 and 7 with the thiocabonyl group at position cently described10 zwitterionic compounds 2 and 3 in the
2 of the oxazole system were more stable than the analo- synthesis of pharmacologically interesting fused hetero-
gous compounds 4 and 5, which decomposed during puri- cyclic systems. Saturated derivatives of 1,3-oxazolidin-2-
fication. Generally yields of the pure products 4 and 5 one[3,4-a][1,3]diazepine, as well as 1,3-oxazolidin-2-
were lower than 6 and 7 (Table 1).
one[3,4-a]pyrimidine have not been described in the liter-
ature previously. Hence we believe that this is an attrac-
tive and worthwhile method, which can be applied to the
construction of these and other novel heterocyclic sys-
tems.
HN
NH
N
N
S
H3C
OH
S
References
H3C
O
Ar-HN-SC
Ar-N
(1) Yukio, H.; Yoichi, N.; Keiji, Y.; Akihiro, F.; Tetsuya, T. J.
Chem. Soc., Chem. Commun. 1995, 1, 49.
(2) Sahu, R. K.; Magan, A.; Gupta, B.; Sondhi, S. M.; Srimal, R.
C.; Patnaik, G. K. Phosphorus, Sulfur Silicon Relat. Elem.
1994, 88, 45.
CSCl2
6 a, b
2 a, b
NaHCO3
(3) Kappe, C. O. J. Org. Chem. 1997, 62, 3109.
(4) Wehner, W.; Friedrich, H. H. Ger. Offen. DE 19,915,388,
2000.
(5) Elliott, R. L.; Pireh, D.; Griesgraber, G.; Nilius, A. M.;
Ewing, P. J. J. Med. Chem. 1998, 41, 1651.
(6) Agouridas, C.; Denis, A.; Auger, J. M.; Benedetti, Y.;
Bonnefoy, A. J. Med. Chem. 1998, 41, 4080.
(7) Elliott, R. L.; Pireh, D.; Nilius, A. M.; Johnson, P. M.;
Flamm, R. K. Bioorg. Med. Chem. Lett. 1997, 7, 641.
(8) Keiichiro, H.; Yukihisa, K.; Tomonari, K.; Hiroshi, T. J.
Chem. Soc., Perkin Trans. 2 1992, 621.
HN
NH
N
N
S
H3C
OH
S
H3C
O
Ar-HN-SC
Ar-N
Ar = a: Ph; b: C6H4Cl-p
3 a, b
Scheme 2
7 a, b
The structures of compounds 4–7 were confirmed by
(9) Zaleska, B.; Socha, R.; Ciechanowicz–Rutkowska, M.;
Pilati, T. Monats. Chem. 2000, 131, 1151.
(10) Zaleska, B.; Bazanek, T.; Socha, R.; Karelus, M.;
Grochowski, J.; Serda, P. J. Org. Chem. 2002, 67, 4526.
1H and 13C NMR spectra, MS and microanalysis.14 In
1
the H NMR spectra of compounds 4 and 5, as well as 6
and 7, the signal for two equivalent polar NH groups at
Table 1 Yields of Compounds 4–7 (%)
Reagents
4a–7a: Ar = Ph
4b–7b: Ar = p-C6H4Cl
Isocyanates R-NCO
2a 4a
45
3a 5a
2a 6a
3a 7a
2b 4b
3b 5b
2b 6b
3b 7b
R1 = Ph
38
32
30
40
–
–
–
20
20
18
24
–
23
21
20
24
–
–
–
R2 = naphthyl
R3 = p-C6H4Cl
R4 = cyclohexyl
thiophosgene
42
–
–
–
–
38
–
–
–
–
49
–
–
–
–
–
80
70
59
66
Synlett 2002, No. 11, 1831–1834 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Synthesis of Heterocyclic Systems
1833
(11) General procedure for the preparation of zwitterionic com-
pounds 2 and 3: A solution of 0.5 g (1.52 mmol) 1 and 3.04
mmol of the corresponding diamine in toluene was heated
for 5 min. Cooling the mixture yielded colorless crystals,
which were purified by recrystallization from ethanol.
(12) General procedure for the preparation of [1,3]oxazolo[3,4-
a]pyrimidin-6-one derivatives 4 and [1,3]oxazolo[3,4-
a][1,3]diazepin-7-one derivatives 5 using phenylisocyanate:
The corresponding zwitterionic compound 2 or 3 (1 mmol)
was dissolved in toluene at 100 °C and 2 mmol of phenyl
isocyanate was added. The mixture was heated under reflux
for 15 minutes. After cooling in an ice bath, the mixture was
filtered to remove the N,N -diphenylurea. Toluene was
removed under reduced pressure and the crude product was
purified by column chromatography (Al2O3, CCl4:acetone
5:1) and then crystallized from CCl4.
C14H15N3O2S; MW 289.4; mp 130–131 °C; (% C, H, N):
calcd: 58.11, 5.22, 14.52; found: 58.34, 5.05, 14.43; IR
(KBr): (cm–1) = 3262, 3205, 1808, 1790, 1689, 1083; 1H
NMR (CDCl3): (ppm) = 11.03 (s, 1 H, NH), 7.80 (d, 2 H,
Ph, J = 8.4 Hz), 7.41 (t, 2 H, Ph, J = 8.4, Hz), 7.27 (t, 1 H,
Ph, J = 8.4 Hz), 3.56–3.72 (m, 4 H, 2 N-CH2), 1.96 (s, 3 H,
CH3), 1.87–1.93 (m, 2 H, C-CH2-C); 13C NMR (CDCl3):
(ppm) = 193.1 (C=S), 154.9 (C=O), 152.6 (C=N), 138.1,
128.9, 126.9, 122.8 (Ph), 86.3 (C-O), 44.5 (N-CH2), 38.8 (N-
CH2), 28.4 (CH3), 18.8 (CH2); MS (EI): m/z (%) = 289 (6.09)
M+, 154(100) M+ – PhNCS, 135 (19.73) PhNCS+, 126
(15.41) M+ – PhNCS – CCH3, 109 (3.13) M+ – PhNCS –
CO2, 84 (18.15) CH2CH2CH2NCO, 77 (14.64) Ph.
2,3,4,6-Tetrahydro-8-methyl-8-(N-p-chlorophenyl-
thiocarbamoyl)-8H-[1,3]oxazolo[3,4-a]pyrimidin-6-one
(4b): C14H14ClN3O2S; MW 323.8; mp 154–155 °C; (% C, H,
N): calcd: 51.93, 4.36, 12.98; found: 52.08, 4.35, 12.98; IR
(KBr): (cm–1) = 3183, 3111, 1800, 1694, 1081; 1H NMR
(CDCl3): (ppm) = 11.03 (s, 1 H, NH), 7.76 (d, 2 H, p-
chlorophenyl, J = 8.5 Hz), 7.36 (d, 2 H, p-chlorophenyl, J =
8.5 Hz), 3.56–3.72 (m, 4 H, 2 N-CH2), 1.95 (s, 3 H, CH3),
1.88–1.93 (m, 2 H, C-CH2-C); 13C NMR (CDCl3): (ppm) =
193.4 (C=S), 154.9 (C=O), 152.5 (C=N), 136.7, 131.9,
129.0, 124.0 (p-chlorophenyl), 86.3 (C-O), 44.5 (N-CH2),
38.9 (N-CH2), 28.5 (CH3), 18.8 (CH2); MS (EI): m/z (%) =
323 (2.3) M+, 169 (24.5) Cl-C6H4-NCS+, 154(100) M+ – Cl-
C6H4-NCS, 126 (16.4) M+ – Cl-C6H4-NCS – CCH3, 111
(13) General procedure for the preparation of [1,3]oxazolo[3,4-
a]pyrimidine-6-thione derivatives 6 and [1,3]oxazolo[3,4-
a][1,3]diazepine-7-thione derivatives 7:
The corresponding zwitterionic compound 2 and 3 (1 mmol)
was dissolved in 20 mL of chloroform at 0 °C, and 10 mL of
water and 2 mmol of sodium bicarbonate were added. While
stirring, 1 mmol of thiophosgene was added and the mixture
was stirred vigorously for 40 minutes. The organic phase
was then separated and evaporated under reduced pressure,
at room temperature. The crude product was purified by
column chromatography (Al2O3–CCl4: acetone 5:1) and then
crystallized from CCl4.
+
(14.1) Cl-C6H4 , 84 (28.3) CH2CH2CH2NCO.
(14) Physical data: Melting points were determined on an
electrothermal IA9000 digital melting point apparatus and
are uncorrected. The IR spectra were obtained on a Bruker
IFS 48 spectrometer at room temperature. 1H and 13C NMR
spectra were recorded with a Bruker AMX 500 NMR
spectrometer using TMS as internal standard. Chemical
shifts are reported in ppm downfield from TMS.
2,3,4,5,7,9-Hexahydro-9-methyl-9-(N-phenylthio-
carbamoyl)-[1,3]oxazolo[3,4-a][1,3]diazepin-7-one (5a):
C15H17N3O2S; MW 303.4; mp 114–115 °C; (% C, H, N):
calcd: 59.39, 5.65, 13.85; found: 59.16, 5.51, 13.71; IR
(KBr): (cm–1) = 3179, 1798, 1694, 1087; 1H NMR (CDCl3):
(ppm) = 11.61 (s, 1 H, NH), 7.82–7.23 (m, 5 H, Ph), 3.78–
3.83 (m, 2 H, N-CH2), 3.66–3.77 (m, 2 H, N-CH2), 1.95–
1.99 (m, 4 H, C-CH2CH2-C), 1.91 (s, 3 H, CH3); 13C NMR
(CDCl3): (ppm) = 193.8 (C=S), 154.2 (C=O), 153.7 (C=N),
138.5, 128.9, 126.7, 122.4 (Ph), 85.1 (C-O), 50.9 (N-CH2),
46.4 (N-CH2), 29.7 (CH2), 29.2 (CH3), 26.2 (CH2); MS (EI):
m/z (%) = 303(3) M+, 168 (100) M+ – PhNCS, 140 (8) M+ –
PhNCS – CCH3, 135 (63) PhNCS+, 123 (23) M+ – PhNCS –
CO2, 98 (18) CH2CH2CH2CH2NCO.
Spectral data for compounds 2a and 3a are described in our
recent work. 10
2-Hydroxy-2-methyl-2-(1,3,4,5,6-pentahydropyrimidin-
2-ylium)-1-(p-chlorophenylimino)thiolate (2b):
C13H16ClN3OS; MW 297.8; mp 196–197 °C; (% C, H, N):
calcd: 52.43, 5.42, 14.11; found: 52.43, 5.27, 14.07; IR
(KBr): (cm–1) = 3323, 2885, 1661; 1H NMR (DMSO-d6):
(ppm) = 7.75–10.00 broad (s, 2 H, 2 NH), 7.38 (d, 2 H,
p-chlorophenyl, J = 8.8 Hz), 7.22 (d, 2 H, p-chlorophenyl,
J = 8.8 Hz), 3.47 (t, 4 H, 2 N-CH2, J = 5.8 Hz), 1.93
(quintet, 2 H, CH2, J = 5.8 Hz), 1.74 (s, 3 H, CH3); 13C NMR
(DMSO-d6): (ppm) = 186.4 (C-S), 166.2 (N-C-N), 151.7,
127.6, 125.3, 123.9 (p-chlorophenyl), 74.9 (C-O), 38.4 (N-
CH2), 28.3 (CH3), 17.8 (CH2); MS (EI): m/z (%) = 298 (0.3)
M+, 169 (2.8) Cl-C6H4-NCS+, 127 (100) M+ – Cl-C6H4-NCS,
2,3,4,5,7,9-Hexahydro-9-methyl-9-(N-p-chlorophenyl-
thiocarbamoyl)-[1,3]oxazolo[3,4-a][1,3]diazepin-7-one
(5b): C15H16ClN3O2S; MW 337.8; mp 128–129 °C; (% C, H,
N): calcd: 53.33, 4.77, 12.44; found: 53.40, 4.88, 12.39; IR
(KBr): (cm–1) = 3164, 3100, 1792, 1702, 1089; 1H NMR
(CDCl3): (ppm) = 11.68 (s, 1 H, NH), 7.77 (d, 2 H, p-
chlorophenyl, J = 8.5 Hz), 7.35 (d, 2 H, p-chlorophenyl, J =
8.5 Hz), 3.78–3.82 (m, 2 H, N-CH2), 3.67–3.73 (m, 2 H, N-
CH2), 1.94–1.98 (m, 4 H, C-CH2CH2-C), 1.90 (s, 3 H, CH3);
13C NMR (CDCl3): (ppm) = 194.1 (C=S), 154.1 (C=O),
153.7 (C=N), 137.0, 131.6, 129.0, 123.6 (p-chlorophenyl),
85.1 (C-O), 50.9 (N-CH2), 46.4 (N-CH2), 29.7 (CH2), 29.3
(CH3), 26.2 (CH2); MS (EI): m/z (%) = 337 (15) M+, 169
(100) Cl-C6H4-NCS+, 168 (59.5) M+ – Cl-C6H4-NCS, 123
+
111 (5.3) Cl-C6H4 , 85 (4.5) M+ – Cl-C6H4-NCS – CH3COH.
2-Hydroxy-2-methyl-2-(1,3,4,5,6,7-hexahydro-1,3-
diazepin-2-ylium)-1-(p-chlorophenylimino)thiolate (3b):
C14H18ClN3OS; MW 311.8; mp 166–167 °C; (% C, H, N):
calcd: 53.92, 5.82, 13.48; found: 53.80, 5.56, 13.49; IR
(KBr): (cm–1) = 3278, 2929, 2862, 1680; 1H NMR (DMSO-
d6): (ppm) = 8.5–9.5 broad (s, 2 H, 2 NH), 7.25 (d, 2 H,
p-chlorophenyl, J = 8.8 Hz), 7.09 (d, 2 H, p-chlorophenyl, J
= 8.8 Hz), 3.55–3.61 (m, 4 H, 2 N-CH2-C), 1.84–1.93 (m,
4 H, C-CH2-CH2-C), 1.61 (s, 3 H, CH3); 13C NMR (DMSO-
d6): (ppm) = 186.8 (C-S), 171.2 (N-C-N), 151.6, 127.7,
125.5, 123.8 (p-chlorophenyl), 75.6 (C-O), 42.7 (N-CH2),
28.4 (CH3), 25.7 (CH2); MS (EI): m/z (%) = 311 (0.1) M+,
169 (3.1) Cl-C6H4-NCS+, 141(100) M+ – Cl-C6H4-NCS, 111
+
(41.3) M+ – Cl-C6H4-NCS – CO2, 111 (29.5) Cl-C6H4 , 98
(6.2) CH2CH2CH2CH2NCO.
2,3,4,6-Tetrahydro-8-methyl-8-(N-phenylthio-
carbamoyl)-8H-[1,3]oxazolo[3,4-a]pyrimidine-6-thione
(6a): C14H15N3OS2; MW 305.4; mp 113–114 °C; (% C, H,
N): calcd: 55.06, 4.95, 13.76; found: 54.96, 4.91, 13.77; IR
(KBr): (cm–1) = 3271, 3206, 1697; 1H NMR (CDCl3):
(ppm) = 10.55 (s, 1 H, NH), 7.78 (d, 2 H, Ph, J = 8.5 Hz),
7.40 (t, 2 H, Ph, J = 8.5 Hz), 7.27 (t, 1 H, Ph, J = 8.5 Hz),
3.79–3.92 (m, 2 H, N-CH2), 3.58–3.69 (m, 2 H, N-CH2),
2.01 (s, 3 H, CH3), 1.93–1.97 (m, 2 H, C-CH2-C); 13C NMR
(6.9) Cl-C6H4 , 99 (14.9) M+ – Cl-C6H4-NCS – CH3COH.
+
2,3,4,6-Tetrahydro-8-methyl-8-(N-phenylthio-carba-
moyl)-8H-[1,3]oxazolo[3,4-a]pyrimidin-6-one (4a):
Synlett 2002, No. 11, 1831–1834 ISSN 0936-5214 © Thieme Stuttgart · New York

1834
B. Zaleska, M. Karelus
LETTER
(CDCl3): (ppm) = 192.2 (C=S), 185.0 (C=S, ester), 153.8
(C=N), 137.9, 128.9, 127.0, 122.9 (Ph), 89.9 (C-O), 44.7 (N-
CH2), 42.2 (N-CH2), 27.9 (CH3), 19.0 (CH2); MS (EI): m/z
(%) = 306 (58.00) M+, 170(100) M+ – PhNCS, 135 (85.79)
PhNCS+, 110 (10.55) M+ – PhNCS – COS, 77 (14.64) Ph.
2,3,4,6-Tetrahydro-8-methyl-8-(N-p-chlorophenylthio-
carbamoyl)-8H-[1,3]oxazolo[3,4-a]pyrimidine-6-thione
(6b): C14H14ClN3OS2; MW 339.9; mp 126–127 °C; (% C, H,
N): calcd: 49.48, 4.15, 12.36; found: 49.68, 3.87, 12.51; IR
(KBr): (cm–1) = 3180, 3121, 1695; 1H NMR (CDCl3):
(ppm) = 10.61 (s, 1 H, NH), 7.75 (d, 2 H, p-chlorophenyl,
J = 8.5 Hz), 7.36 (d, 2 H, p-chlorophenyl, J = 8.5 Hz), 3.79–
3.92 (m, 2 H, N-CH2), 3.57–3.69 (m, 2 H, N-CH2), 1.99 (s, 3
H, CH3), 1.92–1.98 (m, 2 H, C-CH2-C); 13C NMR (CDCl3):
(ppm) = 192.5 (C=S), 184.9 (C=S, ester), 153.9 (C=N),
136.4, 132.1, 129.0, 124.2 (p-chlorophenyl), 89.8 (C-O),
44.7 (N-CH2), 42.2 (N-CH2), 28.0 (CH3), 19.0 (CH2); MS
(EI): m/z (%) = 169 (90.62) Cl-C6H4-NCS+, 170 (64.52) M+
(ppm) = 11.10 (s, 1 H, NH), 7.79 (d, 2 H, Ph, J = 8.5), 7.41
(t, 2 H, Ph, J = 8.5 Hz), 7.26 (t, 1 H, Ph, J = 8.5 Hz), 3.97–
4.14 (m, 2 H, N-CH2), 3.86–3.87 (m, 2 H, N-CH2), 1.99–
2.03 (m, 4 H, CH2CH2), 1.94 (s, 3 H, CH3); 13C NMR
(CDCl3): (ppm) = 192.85 (C=S), 187.7 (C=S, ester), 152.6
(C=N), 138.2, 128.9, 126.8, 122.6 (Ph), 88.2 (C-O), 50.4 (N-
CH2), 49.9 (N-CH2), 28.9 (CH2), 28.5 (CH3), 25.5 (CH2);
MS (EI): m/z (%) = 184 (12.04) M+ – PhNCS, 135 (10.21)
PhNCS+, 77 (17.87) Ph.
2,3,4,5,7,9-Hexahydro-9-methyl-9-(N-p-chlorophenyl-
thiocarbamoyl)-[1,3]oxazolo[3,4-a][1,3]diazepine-7-
thione (7b): C15H16ClN3OS2; MW 353.9; mp 118–119 °C;
(% C, H, N): calcd: 50.91, 4.56, 11.87; found: 50.88, 4.73,
11.86; IR (KBr): (cm–1) = 3171, 3119, 1694; 1H NMR
(CDCl3): (ppm) = 11.16 (s, 1 H, NH), 7.75 (d, 2 H, p-
chlorophenyl, J = 8.5 Hz), 7.35 (d, 2 H, p-chlorophenyl, J =
8.5 Hz), 3.98–4.20 (m, 2 H, N-CH2), 3.80–3.95 (m, 2 H, N-
CH2), 1.98–2.05 (m, 4 H, C-CH2CH2-C), 1.93 (s, 3 H, CH3);
13C NMR (CDCl3): (ppm) = 193.1 (C=S), 187.6 (C=S,
ester), 152.8 (C=N), 136.7, 131.8, 129.0, 123.8 (p-
+
– Cl-C6H4-NCS, 111 (23.06) Cl-C6H4 .
2,3,4,5,7,9-Hexahydro-9-methyl-9-(N-phenylthio-
carbamoyl)-[1,3]oxazolo[3,4-a][1,3]diazepine-7-thione
(7a): C15H17N3OS2; MW 319.5; mp 102–103 °C; (% C, H,
N): calcd: 56.40, 5.36, 13.15; found: 56.32, 5.49, 13.21; IR
(KBr): (cm–1) = 3193, 3137, 1704; 1H NMR (CDCl3):
chlorophenyl), 88.2 (C-O), 50.4 (N-CH2), 49.9 (N-CH2),
29.0 (CH2), 28.7 (CH3), 25.5 (CH2); MS (EI): m/z (%) = 169
(44.73) Cl-C6H4-NCS+, 184 (16.54) M+ – Cl-C6H4-NCS.
Synlett 2002, No. 11, 1831–1834 ISSN 0936-5214 © Thieme Stuttgart · New York