, 2003, 13(6), 269–271
by crystallization from water; the angle of optical rotation was
–18.52°. Note that stereoisomers 3c and 3'c exhibited opposite
rotation angles, equal melting temperatures, and identical NMR
spectra; that is, they are enantiomers.
In the reactions of compounds 1 with S- and R-N-carbamoyl-
α-amino acids, the products of two side processes were also
found: the rearrangement of 4,5-dihydroxyimidazolidin-2-one 1
into hydantoin 4a and the self-cyclization of N-carbamoyl-α-
amino acids 2a–c into hydantoins 4b–d (Scheme 1). Yields of
4a–d were in the 38–40% region. These processes are well
known, and the resulting hydantoins were described in the lite-
rature.7,8
H(4O)
O(3)
O(4)
H(5)
C(5)
H(1)
C(13)
C(1)
N(4)
H(6N)
O(2)
N(6)
N(2)
C(3)
C(9)
H(4N)
N(8)
H(8N)
C(10)
C(7)
O(1)
C(12)
C(11)
To determine the configurations of asymmetric C(1) and C(5)
atoms in the glycoluriles synthesised, we performed X-ray dif-
fraction analysis of single crystals of the predominant isomers
of compounds 3c,d and minor stereoisomer 3'c.‡
S(1)
Figure 2 The general view of 3'c. The selected bond lengths (Å): N(2)–
C(1) 1.450(3), N(2)–C(3) 1.382(3), N(2)–C(9) 1.463(3), N(4)–C(3)
1.351(4), N(4)–C(5) 1.435(4), N(6)–C(5) 1.439(4), N(6)–C(7) 1.341(4),
N(8)–C(1) 1.445(3), N(8)–C(7) 1.346(4), O(1)–C(3) 1.223(4), O(2)–C(7)
1.231(4); bond angles (°): N(8)–C(1)–N(2) 115.0(2), N(8)–C(1)–C(5)
102.4(2), N(2)–C(1)–C(5) 103.9(2), C(3)–N(2)–C(1) 111.0(2), C(3)–N(2)–
C(9) 121.9(2), C(1)–N(2)–C(9) 118.5(2), O(1)–C(3)–N(4) 125.6(2), O(1)–
C(3)–N(2) 126.2(3), N(4)–C(3)–N(2) 108.2(2), C(3)–N(4)–C(5) 113.2(2),
N(4)–C(5)–N(6) 114.7(3), N(4)–C(5)–C(1) 103.2(2), N(6)–C(5)–C(1)
103.5(2), C(7)–N(6)–C(5) 112.4(3), O(2)–C(7)–N(6) 125.2(3), O(2)–C(7)–
N(8) 126.1(3), N(6)–C(7)–N(8) 108.7(3), C(7)–N(8)–C(1) 112.7(3). Con-
formation: C(1)N(2)C(3)N(4)C(5) cycle – envelope [deviation of C(3)
0.09 Å], C(1)C(5)N(6)C(7)N(8) cycle – envelope [deviation of C(7) 0.06 Å].
The main geometry parameters in 3c, 3'c and 3d are similar.‡
The torsion angles H(1)C(1)C(5)H(5) are 2° and 12° in 3d
and 3c, respectively. The conformation of five-membered rings
is a flattened envelope. In the ring with the substituted nitro-
gen atom, the C(3) atom projects out of the plane, whereas the
C(5) or C(7) atom projects out of the plane in the other ring
(Figures 1–3). Nitrogen atoms are planar with an insignificant
pyramidalization of the substituted N(2) atom [the sum of
angles at N(2) varied from 351.7(2)° to 357.2(2)°].
The presence of a great number of proton donors and proton
acceptors in the molecules resulted in a complex supramole-
cular organization in crystals. In this case, despite considerable
differences, the systems of hydrogen bonds in the three test
compounds were somewhat similar. Thus, the H(6N) atoms in
all of the structures participate in intermolecular H-bonds with
O(1) atoms [N(6)···O(1) varied from 2.876(2) to 3.001(2) Å].
Moreover, in 3c and 3'c, the H-bond systems for the H(4N)
atom [N(4)–H(4N)···O(3)] and the hydroxyl group [O(4)–
H(4O)···O(2)] are coincident, whereas the H(8N) atom partici-
†
All new compounds exhibited satisfactory elemental analyses, and
their structures were confirmed by IR, H and 13C NMR spectroscopy.
1
1H and 13C NMR spectra were recorded on Bruker WM-250 (250 MHz)
and Bruker AM-300 (75.5 MHz) spectrometers, respectively. Chemical
shifts were measured with reference to the residual protons of a
[2H6]DMSO solvent (d 2.50 ppm).
Initial 4,5-dihydroxyimidazolidin-2-one 1 was synthesised according
to a known method from urea and glyoxal;9 N-carbamoyl-α-amino
acids 2a–d were synthesised analogously to the published methods from
α-amino acids and KOCN.10,11
2-[(1R,5S)+(1S,5R)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-
yl)]-2(S)-pentanoic acid 3a + 3'a: yield 33%. 1H NMR ([2H6]DMSO) d:
0.81–0.95 (m, 3H, Me), 1.15–1.51 (m, 2H, CH2), 1.63–2.06 (m, 2H,
CH2), 3.85 (dd, 1H, CH, 3J 4.89 Hz, 3J 10.37 Hz) for 3'a, 4.23 (dd, 1H,
CH, J 6.11 Hz, J 9.27 Hz) for 3a, 5.11–5.43 (m, 2H, CH–CH), 7.11,
7.27 7.36. 7.36 7.43, 7.61 (5br. s, 3H, 3NH), 12.61 (br. s, 1H, COOH).
2-[(1R,5S)+(1S,5R)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-
yl)]-2(S)-butanoic acid 3b + 3'b: yield 35%. 1H NMR ([2H6]DMSO) d:
0.81–1.02 (m, 3H, Me), 1.67–2.04 (m, 2H, CH2), 3.78 (dd, 1H, CH,
3J 6.10 Hz, 3J 9.76 Hz) for 3'b, 4.15 (dd, 1H, CH, 3J 4.89 Hz, 3J
10.38 Hz) for 3b, 5.18–5.50 (m, 2H, CH–CH), 7.11, 7.28, 7.33, 7.41,
7.61 (5br. s, 3H, NH), 12.65 (br. s, 1H, COOH).
‡
Crystallographic data for compounds 3c, 3'c and 3d.
The crystal of 3c (C9H14N4O4S) is orthorhombic at 110 K, space
group P212121, a = 8.9981(9) Å, b = 10.808(1) Å, c = 12.589(1) Å, V =
= 1224.2(2) Å3, Z = 4 (Z' = 1), M = 274.30, dcalc = 1.488 g cm–3,
m(MoKα) = 2.79 cm–1, F(000) = 576.
The crystal of 3'c (C9H14N4O4S) is orthorhombic at 298 K, space
group P212121, a = 6.084(5) Å, b = 9.744(7) Å, c = 20.607(17) Å, V =
= 1221.7(16) Å3, Z = 4 (Z' = 1), M = 274.30, dcalc = 1.491 g cm–3,
m(MoKα) = 2.79 cm–1, F(000) = 576.
The crystal of 3d (C11H16N4O6) is trigonal at 298 K, space group
P3221, a = 10.492(2) Å, c = 22.149(4) Å, V = 2111.5(6) Å3, Z = 6
(Z' = 1), M = 300.28, dcalc = 1.417 g cm–3, m(MoKα) = 1.16 cm–1,
F(000) = 948.
Intensities of 10347 (3c), 2075 (3'c) and 3032 (3d) reflections were
measured with a Smart 1000 CCD diffractometer [l(MoKα) = 0.71072 Å,
w-scan with a 10 s exposure, 2q < 60°] at 100 K (3c) and with Siemens
P3/PC [l(MoKα) = 0.71072 Å, q/2q scan, 2q < 60° and 52°] at 298 K
(3'c and 3e), 3582 (3c), 2075 (3'c) and 2739 (3d) independent reflec-
tions were used in the further refinement. The structures were solved by
a direct method and refined by the full-matrix least-squares technique
against F2 in the anisotropic-isotropic approximation. The analysis of
the Fourier synthesis has revealed that ester groups in 3d are disordered.
The absolute configurations of 3c and 3'c were determined on the basis
of the Flack parameter. The refinement converged to wR2 = 0.0827 and
GOF = 1.043 for all independent reflections [R1 = 0.0364 was calculated
against F for 3245 observed reflections with I > 2s(I)] for 3c; to wR2 =
= 0.1419 and GOF = 1.025 for all independent reflections [R1 = 0.0492
was calculated against F for 1621 observed reflections with I > 2s(I)]
for 3'c and to wR2 = 0.1550 and GOF = 0.954 for all independent reflec-
tions [R1 = 0.0552 was calculated against F for 1828 observed reflections
with I > 2s(I)] for 3d. All calculations were performed using SHELXTL
PLUS 5.0.
Atomic coordinates, bond lengths, bond angles and thermal param-
eters have been deposited at the Cambridge Crystallographic Data Centre
conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336 033; or deposit@ccdc.cam.ac.uk).
Any request to the CCDC for data should quote the full literature citation
and CCDC reference number 227399–227401. For details, see ‘Notice to
Authors’, Mendeleev Commun., Issue 1, 2003.
3
3
(+)-2-[(1R,5S)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-yl)]-2(S)-
4-methylthiobutanoic acid 3c: yield 37%, mp 256–258 °C (decomp.), [a]D20
+18.50° (c 2; 1 N NaOH). 1H NMR ([2H6]DMSO) d: 2.05–2.17 (m, 5H,
3
Me + CH2), 2.36–2.64 (m, 2H, CH2), 4.47 (dd, 1H, CH, 3J 9.4 Hz, J
6.3 Hz), 5.29 [dt, 1H, C(1)H, 3J 8.44 0.04 Hz, 3J 1.7 Hz], 5.41 [dd, 1H,
3
3
C(5)H, J 8.44 0.04 Hz, J 2.4 Hz], 7.25 (br. s, 2H, 2NH), 7.48 (br. s,
1H, NH), 12.81 (br. s, 1H, OH). 13C NMR ([2H6]DMSO) d: 14.64 (Me),
28.79 (CH2), 30.28 (CH2), 53.18 (CH), 62.99 (CH), 67.48 (CH), 160.02
(CO), 161.53 (CO), 173.01 (COOH).
(–)-2-[(1S,5R)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-yl)]-2(S)-
4-methylthiobutanoic acid 3'c: yield 6%, mp 233–235 °C (decomp.), [a]D20
–77.78° (c 2; 1 N NaOH). 1H NMR ([2H6]DMSO) d: 2.10–2.19 (m, 5H,
Me + CH2), 2.51–2.61 (m, 2H, CH2), 4.07 (dd, 1H, CH, 3J 4.89 Hz,
3J 10.36 Hz), 5.29 [br. d, 1H, C(1)H, 3J 8.16 0.03 Hz], 5.34 [br. d, 1H,
3
C(5)H, J 8.16 0.03 Hz], 7.28 (s, 1H, NH), 7.38 (s, 1H, NH), 7.51 (s,
1H, NH), 12.75 (br. s, 1H, OH).
(–)-2-[(1S,5R)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]oct-2-yl)]-2(R)-
4-methylthiobutanoic acid 3''c: yield 37%, mp 256–258 °C (decomp.), [a]2D0
–18.50° (c 2; 1 N NaOH). For 1H NMR and 13C NMR ([2H6]DMSO) see
3c.
Dimethyl ester of 2-[(1R,5S)-(3,7-Dioxo-2,4,6,8-tetraazabicyclo[3.3.0]-
oct-2-yl)]-2(S)-pentanedioic acid 3d: yield 34%, mp 248–250 °C.
1H NMR ([2H6]DMSO) d: 2.00–2.21 (m, 2H, CH2), 2.28–2.46 (m, 2H,
CH2), 3.59 (s, 3H, OMe), 3.65 (s, 3H, OMe), 4.39 (dd, 1H, CH, 3J
5.15 Hz, 3J 11.03 Hz), 5.24 [br. d, 1H, C(1)H, 3J 8.32 0.02 Hz], 5.48
[br. d, 1H, C(5)H, 3J 8.32 0.02 Hz], 7.36 (br. s, 2H, 2NH), 7.64 (s, 1H,
NH). 13C NMR ([2H6]DMSO) d: 24.35 (CH2), 29.85 (CH2), 51.31 (Me),
52.14 (Me), 53.47 (CH), 62.82 (CH), 67.22 (CH), 159.53 (CO), 161.12
(CO), 171.27 (COOMe), 172.58 (COOMe).
– 270 –