Pyramidal nitrogen in the crystal of N-[(benzoyl)-(hydroxy)methyl]-N- benzyloxy-N'-(2-bromophenyl)urea

Article abstract of DOI:10.1016/j.mencom.2010.05.015

Phenylglyoxal reacts with N-benzyloxy-N'-(2-bromophenyl)urea forming N-[(benzoyl)(hydroxy)methyl]-N-benzyloxy-N'-(2-bromophenyl)urea. As it was found by XRD study, the molecules of the latter in crystal exist in two forms which vary in a different degree

Full text of DOI:10.1016/j.mencom.2010.05.015

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 167–169
Pyramidal nitrogen in the crystal of N-[(benzoyl)-
(hydroxy)methyl]-N-benzyloxy-N'-(2-bromophenyl)urea†
Remir G. Kostyanovsky,*a Vasiliy G. Shtamburg,b Oleg V. Shishkin,c Roman I. Zubatyuk,c
Victor V. Shtamburg,d Andrey A. Anishchenkod and Alexander V. Mazepae
a N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 495 651 2191; e-mail: kost@center.chph.ras.ru
b Ukrainian State University of Chemical Technology, 49038 Dnepropetrovsk, Ukraine.
E-mail: stamburg@gmail.com
c STC ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine, 61001 Kharkov, Ukraine.
E-mail: shishkin@xray.isc.kharkov.com
d Department of Chemistry, Dnepropetrovsk National University, 49050 Dnepropetrovsk, Ukraine.
E-mail: koloxai@gmail.com
e A. V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine, 65080 Odessa, Ukraine.
E-mail: chemtor@paco.net
DOI: 10.1016/j.mencom.2010.05.015
Phenylglyoxal reacts with N-benzyloxy-N'-(2-bromophenyl)urea forming N-[(benzoyl)(hydroxy)methyl]-N-benzyloxy-N'-
(2-bromophenyl)urea. As it was found by XRD study, the molecules of the latter in crystal exist in two forms which vary in a
different degree of pyramidality of the same nitrogen atom. Reactions of N-ethoxy-N'-phenylurea and N-benzyloxy-N'-(4-nitro-
phenyl)urea with phenylglyoxal lead to cyclic products.
Arylglyoxals react with N-hydroxyurea in neutral aqueous media
C(O)Ph
to produce 5-aryl-3-hydroxyimidazolidine-2,4-diones2 at the final
PhC(O)CHO
Br
stage. The reaction proceeds via intermediate acyclic substituted
N-hydroxyureas and then 5-aryl-3,4,5-trihydroxyimidazolidin-
2-ones. Some of these intermediates have been isolated and
their structures have been established. XRD study revealed
the cis-orientation of 4-OH and 5-OH groups in monocrystal of
5-(4-chlorophenyl)-3,4,5-trihydroxyimidazolidin-2-one.2 Mean-
while, phenylglyoxal reacts with N-alkoxyureas in organic
solvents to afford 3-alkoxy-5-phenylimidazolidine-2,4-diones.3
In continuation of these investigations, we have studied reaction
of phenylglyoxal with N-alkoxy-N'-arylureas.
H
Br
H
OH
CH2Cl2, room
temperature
N
N
HN
NHOBn
NHOEt
OBn
O
O
1
2
O
Ph
H
PhHN
PhC(O)CHO
N
OEt
N
CH2Cl2, room
temperature
Ph
O
O
Reaction between phenylglyoxal and N-benzyloxy-N'-(2-bromo-
phenyl)urea 1 in dichloromethane solution at room tempera-
ture gives only acyclic N-[(benzoyl)(hydroxy)methyl]-N-benzyl-
oxy-N'-(2-bromophenyl)urea 2 (Scheme 1). Probably, the
bulky ortho-bromo substitutent retards the further cyclization
into expected 3-benzyloxy-1-(2-bromophenyl)-4,5-dihydroxy-
5-phenylimidazolidin-2-one.
3
5
H
Ph
OH
HO
N
OBn
N
4-NO2C6H4
NO2
O
In contrast, analogous ureas 3, 4 bearing aryl moieties depriving
of ortho substituent react with phenylglyoxal to yield cyclic
products (Scheme 1).‡ N-Ethoxy-N'-phenylurea 3 is transformed
into hidantoin 5, while N-benzyloxy-N'-(4-nitrophenyl)urea 4
6
PhC(O)CHO
+
CH2Cl2, room
temperature
O
Ph
HN
NHOBn
H
N
OBn
N
†
O
Asymmetric Nitrogen. Part 105; previous communication, see ref. 1.
N-Benzyloxy-N'-(2-bromophenyl)urea 1. The solution of o-bromo-
4-NO2C6H4
O
‡
4
7
phenylisocyanate (1.230 g, 6.215 mmol) in benzene (8 ml) was added to
the solution of benzyloxyamine (0.985 g, 0.800 mmol) in benzene (8 ml),
reaction mixture was kept at 23 °C for 70 h, then the precipitate was
filtered off and washed with hexane, giving 1.661 g (83%) of urea 1,
Scheme 1
along with the similar hidantoin 7 gives also dihydroxyimidazo-
lidinone 6.
1
colourless crystals, mp 113–114 °C. H NMR (300 MHz, [2H6]DMSO)
d: 4.89 (s, 2H, NOCH2), 7.03 [td, 1H, C(4)H, 3J 7.8 Hz, 4J 1.2 Hz], 7.36
[td, 1H, C(5)H, 3J 7.8 Hz, 4J 1.2 Hz], 7.38–7.44 (m, 3H, Ph), 7.48–7.51
(m, 2H, Ph), 7.64 [dd, 1H, C(6)H, 3J 7.8 Hz, 4J 1.2 Hz], 8.01 [dd, 1H,
C(3)H, 3J 7.8 Hz, 4J 1.2 Hz], 8.23 (br. s, 1H, NH), 10.00 (br. s, 1H,
NHO). Found (%): N, 8.78; Br, 24.71. Calc. for C14H13BrN2O2 (%): N,
8.72; Br, 24.88.
Compound 6 was isolated as a single diastereomer probably
having cis-orientation of OH groups, by analogy with 5-(4-
chlorophenyl)-3,4,5-trihydroxyimidazolidin-2-one.2
XRD study of urea 2§ (Figures 1, 2) finally evidenced its
acyclic structure. Asymmetric part of the unit cell contains two
molecules labeled as 2A and 2B, possessing the same relative
– 167 –
© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 167–169
C(20)
C(19)
C(21)
C(22)
C(18)
b
Br(1)
C(17)
C(16)
O(4)
O(3)
C(3)
C(9)
C(4)
C(5)
C(2)
N(2)
C(11)
C(10)
O(2)
a
N(1)
C(15) C(8)
C(1)
C(12)
C(13)
C(7)
C(6)
C(14)
O(1)
0
Figure 2 Structure of molecule 2A.
c
molecule 2A has slightly higher pyramidality degree as com-
pared to the molecule 2B. The sum of bond angles centered on
this atom is 336.0(3)° in the molecule 2A and 341.2(3)° in the
molecule 2B.
The former value is close to that in N-methoxy-N-(pyridinium-
1-yl)urea perchlorate (333.9°)4 containing strongly pyramidal
nitrogen atom. The deviation of the N(1) atom from the plane
of bonded atom is 0.416(3) Å in the molecule 2A [cf. 0.429 Å in
N-methoxy-N-(pyridinium-1-yl)urea perchlorate4] and 0.366(3) Å
in the molecule 2B.
Figure 1 Symmetry of the unique part of the unit cell in the crystal of 2
containing two molecules. Hydrogen atoms were omitted for clarity.
configuration of their chiral centres, namely the saturated carbon
atom C(8) and pyramidal nitrogen N(1). The N(1) atom in the
N-[(Benzoyl)(hydroxy)methyl]-N-benzyloxy-N'-(2-bromophenyl)urea 2.
The solution of phenylglyoxal (0.127 g, 0.944 mmol) in CH2Cl2 (5 ml)
was added to the solution of N-benzyloxy-N'-(2-bromophenyl)urea 1
(0.303 g, 0.944 mmol) in CH2Cl2 (7 ml). The reaction mixture was kept
at 20–23 °C for 46 h, then the solvent was evaporated in vacuo, the residue
was crystallized from benzene–hexane to give 0.345 g (80%) of the product
2, colourless crystals, mp 86–88 °C (THF–hexane). 1H NMR (300 MHz,
CDCl3) d: 4.65 (d, 1H, NOCH2Ph, 3J 10.5 Hz), 4.85 (d, 1H, NOCH2Ph,
3J 10.5 Hz), 4.97 (d, 1H, CHOH, 3J 8.1 Hz), 6.76 (d, 1H, CHOH, 3J 8.1 Hz),
6.97 [td, 1H, C(4)H, 3J 7.5 Hz, 4J 1.2 Hz], 7.30 [dd, 1H, C(6)H, 3J 7.5 Hz,
4J 1.2 Hz], 7.30–7.37 (m, 5H, PhCH2O), 7.52 [t and td, 3H, C(3')H, C(5')H
and C(5)H, 3J 7.5 Hz], 7.65 [t, 1H, C(4')H, 3J 7.5 Hz], 8.16 [d, 2H,
3-Benzyloxy-4,5-dihydroxy-1-(4-nitrophenyl)-5-phenylimidazolidin-2-one
6 and 3-benzyloxy-1-(4-nitrophenyl)-5-phenylimidazolidine-2,4-dione 7.
N-Benzyloxy-N'-(4-nitrophenyl)urea 4 (0.516 g, 1.798 mmol) was added
to the solution of phenylglyoxal (0.307 g, 2.289 mmol) in CH2Cl2 (24 ml),
the reaction mixture was stirred at 20–23 °C for 25 h, the solid was filtered
off, the filtrate was evaporated in vacuo, the residue was dissolved in
benzene (6 ml) and hexane (10 ml) was added. The precipitate was filtered
off, dissolved in THF (6 ml) and Et2O (6 ml) was added. The precipitate
was filtered off, washed by the mixture of Et2O (2 ml) and hexane (2 ml),
yielding 0.040 g (6%) of compound 7, colourless crystals, mp 220–221 °C
3
3
4
C(2')H, C(6')H, J 7.5 Hz], 8.29 [dd, 1H, C(3)H, J 7.5 Hz, J 1.2 Hz],
8.47 (s, 1H, NH). 13C NMR (75 MHz, CDCl3) d: 79.47 (CH2), 80.50
(CHOH), 113.52 [C(2) in C6H4Br], 121.06 [C(3) in C6H4Br], 124.96
[C(6) in C6H4Br], 128.40 [C(4) in C6H4Br], 138.73 [C(5) in C6H4Br],
129.02 [C(2), C(6) in PhCH2], 129.26 [C(3), C(5) in PhCO, PhCH2],
129.54 [C(4) in PhCH2], 132.27 [C(2), C(6) in PhCO], 133.20 [C(1) in
C6H4Br], 133.87 [C(1) in PhCH2], 134.52 [C(4) in PhCO], 135.47 [C(1)
in PhCO], 155.52 (NHCO), 193.58 (PhCO). IR (n/cm–1): 3470 (OH), 3361
(NH), 1705 (C=O), 1690 (C=O). MS (FAB, H+): 455 [M + H]+ (5.0), 240
[M – H2O – BrC6H4N=C=O]+ (100), 91 [Bn]+ (97). Found (%): C, 58.07;
H, 4.15; N, 6.08. Calc. for C22H19BrN2O4 (%): C, 58.04; H, 4.21; N 6.15.
N-Ethoxy-N-phenylurea 3 was obtained from phenylisocyanate and
ethoxyamine in the similar manner as compound 1, colourless crystals,
1
(decomp.). H NMR (300 MHz, CDCl3) d: 5.24 (s, 2H, PhCH2O), 5.38
(s, 1H, CH), 7.12–7.18 (m, 2H, Ph), 7.33–7.42 (m, 6H, Ph and CH2Ph),
7.47–7.50 (m, 2H, Ph), 7.62 [d, 2H, C(2)H, C(6)H in C6H4NO2, 3J 9.3 Hz],
3
8.14 [d, 2H, C(3)H, C(5)H in C6H4NO2, J 9.3 Hz]. IR (n/cm–1): 1784
(C=O), 1730 (C=O), 1510 (NO2), 1335 (NO2). MS (EI), m/z: 403 [M]+
(7.8), 297 [M – PhC(O)H]+ (59.5), 226 (14.6), 91 [Bn]+ (100). Found (%):
C, 65.66; H, 4.53; N, 10.22. Calc. for C22H17N3O5 (%): C, 65.50; H, 4.25;
N, 10.42. The filtrate was concentrated in vacuo and hexane was added.
The precipitate was filtered off, crystallized from CH2Cl2–hexane mixture,
yielding 0.422 g (56%) of the product 6, yellow crystals, mp 139–140 °C
(decomp.). 1H NMR (300 MHz, CDCl3) d: 4.05 (s, 1H, OH), 4.64 (s,
1
yield 60%, mp 101–104 °C. H NMR (300 MHz, CDCl3) d: 1.34 (t, 3H,
NOCH2Me, 3J 7.0 Hz), 3.99 (q, 2H, NOCH2Me, 3J 7.0 Hz), 7.11 [t, 1H,
2
3
3
1H, CH), 4.74 (br. s, 1H, OH), 5.02 (d, 1H, PhCH2O, J 11.1 Hz), 5.09
C(4)H, J 7.8 Hz], 7.34 [t, 2H, C(3)H, C(5)H, J 7.8 Hz], 7.49 [d, 2H,
(d, 1H, PhCH2O, 2J 11.1 Hz), 7.28–7.32 (m, 3H, Ph), 7.33–7.40 (m, 7H,
Ph and CH2Ph), 7.78 [d, 2H, C(2)H, C(6)H in C6H4NO2, 3J 9.3 Hz],
3
C(2)H, C(6)H, J 7.8 Hz], 7.61 (br. s, 1H, NH), 7.71 (br. s, 1H, NHO).
IR (n/cm–1): 3330 (NH), 3195 (NH), 1668 (C=O). MS (FAB, H+): 181
[M + H]+ (100). Found (%): C, 60.11; H, 6.65; N, 15.61. Calc. for
C9H12N2O2 (%): C, 59.99; H, 6.71; N, 15.55.
3
8.05 [d, 2H, C(3)H, C(5)H in C6H4NO2, J 9.3 Hz]. IR (n/cm–1): 3420
(OH), 1725 (C=O), 1510 (NO2), 1330 (NO2). MS (FAB, H+), m/z: 422
[M + H]+ (32.9), 404 [M – OH]+ (4.8), 91 [Bn]+ (100). Found (%): C, 62.55;
H, 4.67; N, 9.82. Calc. for C22H19N3O6 (%): C, 62.70; H, 4.54; N, 9.97.
N-Benzyloxy-N'-(4-nitrophenyl)urea 4 was synthesized from benzyl-
oxyamine and 4-nitrophenylisocyanate in the same manner as ureas 1 and
3, pale yellow crystals, mp 136–138 °C. 1H NMR (300 MHz, [2H6]DMSO)
d: 4.86 (s, 2H, OCH2), 7.34–7.42 (m, 3H, Ph), 7.47–7.49 (m, 2H, Ph),
7.83 [d, 2H, C(2)H, C(6)H, 3J 9.3 Hz], 8.19 [d, 2H, C(3)H, C(5)H,
3J 9.3 Hz], 9.48 (s, 1H, NH), 9.93 (s, 1H, NHO). Found (%): N, 14.72.
Calc. for C14H13N3O4 (%): N, 14.63.
§
X-Ray diffraction data. Single crystals of 2 (C22H19N2O4Br) were
grown from THF–hexane at 5 °C. Diffraction data were collected on
an Xcalibur 3 diffractometer (graphite-monochromated MoKα radiation,
–
2q/q-scan, 2qmax = 52°). At 298 K crystals are triclinic, space group P1,
a = 9.7866(3), b = 13.7761(8) and c = 17.0022(11) Å, a = 67.117(6)°,
b = 76.467(4)°, g = 77.892(4)°, V = 2035.09(19) Å3, M = 455.30, F(000) =
= 928, dcalc = 1.526 g cm–3, Z = 2, m = 2.05 mm–1. 25428 reflections
were collected of which 7945 were unique. The structure was solved by
direct method using the SHELX-97 program package.6 Refinement against
F2 in an anisotropic approximation (the hydrogen atoms were isotropic
in the riding model) by a full matrix least-squares method for 7495
reflections was carried out to wR2 = 0.064 [R1 = 0.037 for 3470 reflec-
tions with F > 4s(F), S = 0.98].
3-Ethoxy-1,5-diphenylimidazolidine-2,4-dione 5. The solution of phenyl-
glyoxal (0.087 g, 0.646 mmol) in CH2Cl2 (8 ml) was added to the solution
of N-ethoxy-N-phenylurea 1 (0.116 g, 0.646 mmol) in CH2Cl2 (4 ml).
The reaction mixture was kept at 20 °C for 70 h, then the solvent was
evaporated in vacuo, the residue was crystallized from Et2O–hexane to
give 0.084 g (46%) of the product 5, colourless crystals, mp 125–126 °C.
1H NMR (300 MHz, CDCl3) d: 1.41 (t, 3H, NOCH2Me, 3J 6.9 Hz), 4.30
(qd, 2H, NOCH2Me, 3J 6.9 Hz, 2J 2.4 Hz), 5.45 (s, 1H, PhCH), 7.12 [t, 1H,
C(4')H, 3J 7.5 Hz], 7.31–7.38 (m, 7H, Ph and Ph'), 7.47 [d, 2H, C(2')H,
CCDC 749267 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2010.
3
C(6')H, J 7.5 Hz]. IR (n/cm–1): 1772 (C=O), 1730 (C=O). MS (FAB,
H+): 297 [M + H]+ (100), 296 [M]+ (44.6). Found (%): C, 69.17; H, 5.62;
N, 9.24. Calc. for C17H16N2O3 (%): C, 68.91; H, 5.44; N, 9.45.
– 168 –

Mendeleev Commun., 2010, 20, 167–169
The first example of two types of pyramidality for the same
nitrogen in the same crystal coexistence was recently reported
for N-chloro-N-ethoxyurea.1
NH group does not form any hydrogen bonds in crystal despite
the presence of proton accepting groups.
In summary, the outcome of the reaction between phenyl-
glyoxal and N-alkoxy-N'-arylureas depends on the substitution
pattern of N'-aryl group. The unusual case of the existence
of the same nitrogen atom in two forms having the different
degrees of pyramidality was found.
Molecules 2A and 2B possess rather similar conformation.
Amide fragment is almost orthogonal to idealized position of
the lone pair of the N(1) atom [the N(2)–C(1)–N(1)–Lp(N1)
torsion angle is 106° in 2A and 99° in 2B]. The C(8)–C(9) bond
has sc-orientation with respect to Lp(N1) [the C(9)–C(8)–N(1)–
Lp(N1) torsion angle is –56° for 2A and –38° for 2B]. Such
conformation of substituent is stabilized by attractive O(1)···H(8)
interaction (the O···H distance is 2.48 Å for 2A, 2.40 Å for 2B).
The C(2)···C(7) and C(10)···C(15) aromatic rings are almost co-
planar to the planes of the N(2)–C(1)–O(1) amide fragment and
the C(9)–O(3) carbonyl group, respectively [the C(1)–N(2)–C(2)–
C(7) and O(3)–C(9)–C(10)–C(11) torsion angles are –17.7(5)°
and –7.3(4)° for 2A, and –12.6(5)° and –6.2(4)° for 2B, respec-
tively].
This work was supported by the Russian Foundation for
Basic Research (grant no. 09-03-00537a).
References
1
O. V. Shishkin, V. G. Shtamburg, R. I. Zubatyuk, D. A. Olefir, A. V. Tsygankov,
A. V. Prosyanik, A. V. Mazepa and R. G. Kostyanovsky, Chirality, 2009,
21, 642.
2 V. G. Shtamburg, A. A. Anishchenko, V. V. Shtamburg, O. V. Shishkin,
R. I. Zubatyuk, A. V. Mazepa, I. M. Rakipov and R. G. Kostyanovsky,
Mendeleev Commun., 2008, 18, 102.
Molecules 2A and 2B are linked in the crystal by the O(2b)–
H(2b)···O(1a) hydrogen bond [H···O 2.15 Å, O···O 2.911(3) Å,
O–H···O 154°]. At the same time, hydroxy group in the molecule
2A forms intramolecular hydrogen bond O(2a)–H(2a)···O(3a)
[H···O 2.14 Å, O···O 2.614(3) Å, O–H···O 117°]. Bromine atoms
form short intermolecular contacts Br(1)···C(9') (1 + x, y, z) 3.41 Å
(contact between two 2A molecules) and 3.49 Å (contact between
two 2B molecules), van der Waals radii sum is 3.68 Å.5 Those
contacts are presumably attractive interactions between lone
pairs of the Br atoms and partially positively charged carbon
atoms. This results from the values of the C(3)–Br(1)···C(9')
(1 + x, y, z) 129° (2A···2A), 133° (2B···2B) angles. Note that
3 V. G. Shtamburg, V. B. Distanov, V. V. Shtamburg, E. A. Klots, A. V.
Mazepa, R. I. Zubatyuk, I. M. Rakipov, B. V. Uspensky, A. A. Anishchenko,
and D. A. Olefir, Visn. Nat. Tech. Univer. ‘KPI’, 2006, no. 13, 152.
4 V. G. Shtamburg, O. V. Shishkin, R. I. Zubatyuk, S. V. Kravchenko, A. V.
Tsygankov, V. V. Shtamburg, V. B. Distanov and R. G. Kostyanovsky,
Mendeleev Commun., 2007, 17, 178.
5 Yu. V. Zefirov, Kristallografiya, 1997, 42, 936 (Crystallography Rep.,
1997, 42, 865).
6 G. Sheldrick, Acta Crystallogr., Sect. A, 2008, 64, 112.
Received: 13th November 2009; Com. 09/3419
– 169 –